Alfred “Fred” Goldberg, Ph.D., (born 1942) is an

American American(s) may refer to: * American, something of, from, or related to the United States of America, commonly known as the "United States" or "America" ** Americans, citizens and nationals of the United States of America ** American ancestry, pe ...

cell biologist Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...

biochemist Biochemists are scientists who are trained in biochemistry. They study chemical processes and chemical transformations in living organisms. Biochemists study DNA, proteins and Cell (biology), cell parts. The word "biochemist" is a portmanteau of ...

and

professor Professor (commonly abbreviated as Prof.) is an Academy, academic rank at university, universities and other post-secondary education and research institutions in most countries. Literally, ''professor'' derives from Latin as a "person who pr ...

Harvard University Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...

. His major discoveries have concerned the mechanisms and physiological importance of

protein degradation Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...

in cells. Of wide impact have been his lab's demonstration that all cells contain a pathway for selectively eliminating

misfolded proteins Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduci ...

, his discoveries about the role of

proteasomes Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by whi ...

in this process and of the enzyme systems catalyzing

protein breakdown In molecular biology, protein catabolism is the breakdown of proteins into smaller peptides and ultimately into amino acids. Protein catabolism is a key function of digestion process. Protein catabolism often begins with pepsin, which converts p ...

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

, his elucidating the mechanisms for

muscle atrophy Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility, aging, malnutrition, medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system. Muscle atrophy leads to muscle weakness ...

and the role of

antigen presentation Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment, now ...

to the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

, and his introduction of proteasome inhibitors now widely used as research tools and in the treatment of

blood cancers Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid tissues (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all ...

Research career

In the 1960s, when Goldberg began his research career, there was extremely little interest in protein degradation.Goldberg, AL. Interview. Curr Biology. 2014; 24(17): pR780–R782. doi: 10.1016/j.cub.2014.08.014Goldberg AL and Dice JF. Intracellular protein degradation in mammalian and bacterial cells. Ann Rev Biochem 1974; 43: 835-869. PubMed PMID: 4604628. However, as a graduate student, Goldberg showed that the loss of

muscle mass Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...

upon

denervation Denervation is any loss of nerve supply regardless of the cause. If the nerves lost to denervation are part of the neuronal communication to a specific function in the body then altered or a loss of physiological functioning can occur. Denervation ...

fasting Fasting is the abstention from eating and sometimes drinking. From a purely physiological context, "fasting" may refer to the metabolic status of a person who has not eaten overnight (see " Breakfast"), or to the metabolic state achieved after ...

occurred primarily through acceleration of protein degradation.Goldberg AL. Protein turnover in skeletal muscle II: Effects of denervation and cortisone on protein catabolism in skeletal muscle. J Biol Chem 1969; 244: 3223-3229. PMID: 5792658. As an Assistant Professor, he decided to focus on this neglected area, and his early studies in

E. coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

and

reticulocytes Reticulocytes are immature red blood cells (RBCs). In the process of erythropoiesis (red blood cell formation), reticulocytes develop and mature in the bone marrow and then circulate for about a day in the blood stream before developing into mat ...

first demonstrated that cells rapidly degrade

as arise through

mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

and errors in

protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...

. These studies defined for the first time many of the key features of intracellular protein degradation, especially its role in protein quality control in eliminating aggregation-prone proteins and its requirement for metabolic energy (ATP). At that time, the lysosome was believed to be the only site for protein degradation in cells. However, in 1977, his lab demonstrated that the rapid breakdown of misfolded proteins in reticulocytes is catalyzed by a non-lysosomal, ATP-dependent system, now called the Ubiquitin Proteasome System. The seminal studies of Hershko,

Ciechanover Aaron Ciechanover ( ; he, אהרן צ'חנובר; born October 1, 1947) is an Israeli biologist who won the Nobel Prize in Chemistry for characterizing the method that cells use to degrade and recycle proteins using ubiquitin. Biography Early ...

, and

Irwin Rose Irwin Allan Rose (July 16, 1926 – June 2, 2015) was an American biologist. Along with Aaron Ciechanover and Avram Hershko, he was awarded the 2004 Nobel Prize in Chemistry for the discovery of ubiquitin-mediated protein degradation. Education ...

on these preparations uncovered the role of ubiquitination in marking such proteins for degradation. Simultaneously, Goldberg and coworkers discovered that protein degradation in

, which lack

ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...

, and

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

involves a new type of

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

, ATP hydrolyzing

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

complexes (

Lon/La, ClpAP, HslUV). They went on to describe their novel mechanisms and induction in stressful states In 1987, his laboratory and Rechsteiner’s described the much larger ATP-dependent

proteolytic Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...

complex that degrades ubiquitinated proteins in

. He named it the

26S proteasome Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by whi ...

to distinguish it from the smaller particle, which he named the

20S proteasome Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by whi ...

, and which they later showed comprises the proteolytic activity of the 26S complex. Their subsequent studies defined many of the proteasome’s novel biochemical features, especially its ATP-dependent mechanism, peptide products, and cellular functions. Their recent research has shown that cellular rates of degradation are controlled in part by regulation of

activity, including by

protein kinases A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a fun ...

. Of major scientific and medical impact was his lab’s development of

proteasome Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by w ...

inhibitors that block degradation in cells.Rock KL, Gramm C, Rothstein L, Clark K, Stein R, et al…Goldberg AL. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell. 1994 Sep 9;78(5):761-71. PubMed PMID: 8087844.Goldberg AL. Development of proteasome inhibitors as research tools and cancer drugs. J Cell Biol. 2012 Nov 12;199(4):583-8. PubMed PMID: 23148232; PubMed Central PMCID: PMC3494858. In collaboration with a small biotech company (Myogenics/Proscript), which he founded, they introduced in 1994 the inhibitor,

MG132 MG132 is a potent, reversible, and cell-permeable proteasome inhibitor ( Ki = 4 nM). It belongs to the class of synthetic peptide aldehydes. It reduces the degradation of ubiquitin-conjugated proteins in mammalian cells and permeable strains of ...

, which has been used in many thousands of publications and has enabled major advances in knowledge about the importance of protein degradation. In introducing these

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

s, they showed that the

is the major site for

in normal

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

s, is critical in activation of inflammatory responses, and is the source of most

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

peptides presented on surface MHC Class 1 molecules, which is critical in immune defense against

viruses A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...

and

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

. His long collaboration with Ken Rock further elucidated this process, identified the unique properties of the

in immune tissues, and defined the roles of cellular peptidases (especially ERAP1) in further processing proteasome products so they fit into MHC Class 1 molecules. Most importantly, Goldberg’s efforts initiated the development by the company of proteasome inhibitor

Bortezomib Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma. This includes multiple myeloma in those who have and have not previously received treatment. It is ...

Velcade Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma. This includes multiple myeloma in those who have and have not previously received treatment. It is ...

, which is used worldwide to treat the common hematological cancer,

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, an ...

. Over 600,000 patients have now been treated with proteasome inhibits, which have extended their life spans and improved their quality of life. Another area where the Goldberg lab has made major contributions concerns the cellular mechanisms of

. His lab first identified factors that suppress

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

protein degradation (e.g.,

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

) or enhance it (e.g., disuse,

cancer cachexia Cachexia () is a complex syndrome associated with an underlying illness, causing ongoing muscle loss that is not entirely reversed with nutritional supplementation. A range of diseases can cause cachexia, most commonly cancer, congestive heart f ...

), and subsequently showed that various types of

muscle wasting Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility, aging, malnutrition, medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system. Muscle atrophy leads to muscle weakness ...

occur through

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

of a common set of atrophy-related genes (atrogenes). They also identified the critical

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

triggering this atrophy program (FoxO3) and elucidated the mechanisms that disassemble the muscles’ contractile apparatus during atrophy.

Education and career

Goldberg was born in 1942 in

Providence, RI Providence is the capital and most populous city of the U.S. state of Rhode Island. One of the oldest cities in New England, it was founded in 1636 by Roger Williams, a Reformed Baptist theologian and religious exile from the Massachusetts Bay ...

and graduated from

Harvard College Harvard College is the undergraduate college of Harvard University, an Ivy League research university in Cambridge, Massachusetts. Founded in 1636, Harvard College is the original school of Harvard University, the oldest institution of higher lea ...

in 1963 ''

magna cum laude Latin honors are a system of Latin phrases used in some colleges and universities to indicate the level of distinction with which an academic degree has been earned. The system is primarily used in the United States. It is also used in some So ...

'' in Biochemical Sciences (where he did his honor’s research in the laboratory of

James Watson James Dewey Watson (born April 6, 1928) is an American molecular biologist, geneticist, and zoologist. In 1953, he co-authored with Francis Crick the academic paper proposing the double helix structure of the DNA molecule. Watson, Crick and ...

). He then spent a year as a Churchill Scholar at

Cambridge University , mottoeng = Literal: From here, light and sacred draughts. Non literal: From this place, we gain enlightenment and precious knowledge. , established = , other_name = The Chancellor, Masters and Schola ...

, where he studied

physiology Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...

, before becoming a medical student at

Harvard Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...

. After two years, he transferred to the Harvard Graduate School and in 1968 received his

PhD PHD or PhD may refer to: * Doctor of Philosophy (PhD), an academic qualification Entertainment * '' PhD: Phantasy Degree'', a Korean comic series * ''Piled Higher and Deeper'', a web comic * Ph.D. (band), a 1980s British group ** Ph.D. (Ph.D. albu ...

Physiology Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...

for studies in the laboratory of HM Goodman. He then joined the faculty at

Harvard Medical School Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...

and rose to become full

Professor Professor (commonly abbreviated as Prof.) is an Academy, academic rank at university, universities and other post-secondary education and research institutions in most countries. Literally, ''professor'' derives from Latin as a "person who pr ...

of Physiology in 1977 and since 1993 Professor of Cell Biology. He also held visiting professorships at University of California (Berkeley) (1976),

Institut Pasteur The Pasteur Institute (french: Institut Pasteur) is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who invented pasteurization and vaccines fo ...

(Paris) (1995), and

(St. John's College) (2012).

Professional honors

*Member of the

American Academy of Arts & Sciences The American Academy of Arts and Sciences (abbreviation: AAA&S) is one of the oldest learned societies in the United States of America, United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bow ...

(2005) *Member of the

National Academy of Medicine The National Academy of Medicine (NAM), formerly called the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, En ...

(2009) *Member of the

National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...

(2015) *Fellow of the

American Physiological Society The American Physiological Society is a non-profit professional society for physiologists. It has nearly 10,000 members, most of whom hold doctoral degrees in medicine, physiology or other health professions. Its mission is to support research and ...

(2015) *Honorary DSc. Degree Watson School of Biology (

Cold Spring Harbor Laboratory Cold Spring Harbor Laboratory (CSHL) is a private, non-profit institution with research programs focusing on cancer, neuroscience, plant biology, genomics, and quantitative biology. It is one of 68 institutions supported by the Cancer Centers ...

) (2009) *Honorary DSc. Degree

Maastricht University Maastricht University (abbreviated as UM; nl, Universiteit Maastricht) is a public research university in Maastricht, Netherlands. Founded in 1976, it is the second youngest of the thirteen Dutch universities. In 2021, 22,383 students studied at ...

(Netherlands) (2011) *Honorary DSc. Degree

University of Barcelona The University of Barcelona ( ca, Universitat de Barcelona, UB; ; es, link=no, Universidad de Barcelona) is a public university located in the city of Barcelona, Catalonia, in Spain. With 63,000 students, it is one of the biggest universities i ...

(Spain) (2014) *Novartis-Drew University Award in Biochemical Science (with T. Maniatis & A. Varshavsky) (1998) *Knobil Prize for Medical Research (Univ Texas School of Medicine, 2007) *Gabbay Award for Biotechnology & Medicine (

Brandeis University , mottoeng = "Truth even unto its innermost parts" , established = , type = Private research university , accreditation = NECHE , president = Ronald D. Liebowitz , pro ...

, 2008) *

Warren Alpert Foundation Prize The Warren Alpert Foundation Prize is awarded annually to scientist(s) whose scientific achievements have led to the prevention, cure or treatment of human diseases or disorders, and/or whose research constitutes a seminal scientific finding that ho ...

(with J. Adams, K. Anderson, P. Richardson) (2012) *Ernest Beutler Prize for Basic Science,

American Society of Hematology The American Society of Hematology (ASH) is a professional organization representing hematologists. It was founded in 1958. Its annual meeting is held in December of every year and has attracted more than 30,000 attendees. The society publishes th ...

(2015) *Passano Prize for Medical Research (

Johns Hopkins University Johns Hopkins University (Johns Hopkins, Hopkins, or JHU) is a private university, private research university in Baltimore, Maryland. Founded in 1876, Johns Hopkins is the oldest research university in the United States and in the western hem ...

, 2021) *Symposium honoring Dr. Goldberg’s “Pioneering contributions to muscle metabolism”, Cachexia Society (Chicago, 2004) *Symposium on “Protein Modification and Degradation” honoring Dr. Goldberg’s 65th Birthday,

Chinese Academy of Medical Sciences Peking Union Medical College (), founded in 1906, is a selective public medical college based in Dongcheng, Beijing, China. It is a Chinese Ministry of Education Double First Class University Plan university. The school is tied to the Peking Un ...

(Beijing, 2007)

Prize Lectureships

*Francis McNaughton Lecture,

McGill University McGill University (french: link=no, Université McGill) is an English-language public research university located in Montreal, Quebec, Canada. Founded in 1821 by royal charter granted by King George IV,Frost, Stanley Brice. ''McGill Universit ...

-Montreal-Neurological Institute (1997) *Bathsheva Rothchild Memorial Lecture,

Israel Academy of Sciences Israel Academy of Sciences and Humanities, based in Jerusalem, was established in 1961 by the State of Israel to foster contact between Israeli scholars in the sciences and humanities and create a think tank for advising the government on r ...

(1998) *Leonardo da Vinci Lecture, San Raffaelle Med School, Milan, Italy (2002) *Fred Fay Memorial Lecture,

University of Massachusetts Medical School The University of Massachusetts Chan Medical School is a public medical school in Worcester, Massachusetts. It is part of the University of Massachusetts system. It is home to three schools: the T.H. Chan School of Medicine, the Morningside Grad ...

(2003) *Severo Ochoa Prize Lecture,

New York University New York University (NYU) is a private research university in New York City. Chartered in 1831 by the New York State Legislature, NYU was founded by a group of New Yorkers led by then-Secretary of the Treasury Albert Gallatin. In 1832, the ...

(2004) *Nobel Forum Lecture,

Karolinska Institute The Karolinska Institute (KI; sv, Karolinska Institutet; sometimes known as the (Royal) Caroline Institute in English) is a research-led medical university in Solna within the Stockholm urban area of Sweden. The Karolinska Institute is consist ...

(Sweden) (2005) *Centennial Lecture,

Biochemical Society The Biochemical Society is a learned society in the United Kingdom in the field of biochemistry, including all the cellular and molecular biosciences. Structure It currently has around 7000 members, two-thirds in the UK. It is affiliated with th ...

, England (2006) *Cristofalo Prize Lecture, Aging Institute (

University of Pennsylvania The University of Pennsylvania (also known as Penn or UPenn) is a private research university in Philadelphia. It is the fourth-oldest institution of higher education in the United States and is ranked among the highest-regarded universitie ...

) (2015) *Benevuto Prize Lecture,

MD Anderson Cancer Center The University of Texas MD Anderson Cancer Center (colloquially MD Anderson Cancer Center) is a comprehensive cancer center in Houston, Texas. It is the largest cancer center in the U.S. and one of the original three comprehensive cancer centers ...

Univ. Texas Medical Center (Houston) (2019)

Family

Since 1970, Prof Goldberg has been married to Dr. Joan Helpern Goldberg, a physician (hematologist). They have two children,

Aaron Goldberg Aaron Goldberg (born April 30, 1974), is an American jazz pianist. Described by ''The New York Times'' as a "post-bop pianist of exemplary taste and range," Goldberg has released five albums as a solo artist and has performed and collaborated wi ...

, a well-known jazz pianist, and Julie B. Goldberg, a software engineer.

Influential publications

#Goldberg AL. Degradation of abnormal proteins in Escherichia coli (protein breakdown-protein structure-mistranslation-amino acid analogs-puromycin). Proc Natl Acad Sci U S A. 1972 Feb;69(2):422-6. PubMed PMID: 4551144; PubMed Central PMCID: PMC426471. #Prouty WF, Goldberg AL. Fate of abnormal proteins in E. coli accumulation in intracellular granules before catabolism. Nat New Biol. 1972 Nov 29;240(100):147-50. PubMed PMID: 4565695. #Goldberg AL, St John AC. Intracellular protein degradation in mammalian and bacterial cells: Part 2. Annu Rev Biochem. 1976;45:747-803. PubMed PMID: 786161. #Goldberg AL and Dice JF. Intracellular protein degradation in mammalian and bacterial cells. Ann Rev Biochem 1974; 43: 835-869. PubMed PMID: 4604628. #Goldberg AL. Protein degradation and protection against misfolded or damaged proteins. Nature. 2003 Dec 18;426(6968):895-9. PubMed PMID: 14685250. #Etlinger JD, Goldberg AL. A soluble ATP-dependent proteolytic system responsible for the degradation of abnormal proteins in reticulocytes. Proc Natl Acad Sci U S A. 1977 Jan;74(1):54-8. PubMed PMID: 264694; PubMed Central PMCID: PMC393195. #Chung CH, Goldberg AL. The product of the lon (capR) gene in Escherichia coli is the ATP-dependent protease, protease La. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4931-5. PubMed PMID: 6458037; PubMed Central PMCID: PMC320299. #Tanaka K, Waxman L and Goldberg AL. ATP serves two distinct roles in protein degradation in reticulocytes, one requiring and one independent of ubiquitin. J Cell Biol 1983; 96: 1580-1585. #Goff SA and Goldberg AL. Production of abnormal proteins in E. coli stimulates transcription of lon and other heat-shock genes. Cell 1985; 41: 587-595. PubMed PMID: 3886165. #Waxman L, Fagan JM, Goldberg AL. Demonstration of two distinct high molecular weight proteases in rabbit reticulocytes, one of which degrades ubiquitin conjugates. J Biol Chem. 1987 Feb 25;262(6):2451-7. PubMed PMID: 3029081. #Hwang BJ, Park WJ, Chung CH, Goldberg AL. Escherichia coli contains a soluble ATP-dependent protease (Ti) distinct from protease La. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5550-4. PubMed PMID: 3303028; PubMed Central PMCID: PMC298900. #Gaczynska M, Rock KL, Goldberg AL. Gamma-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. Nature. 1993 Sep 16;365(6443):264-7. PubMed PMID: 8396732. #Rock KL, Gramm C, Rothstein L, Clark K, Stein R, et al…Goldberg AL. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell. 1994 Sep 9;78(5):761-71. PubMed PMID: 8087844. #Palombella VJ, Rando OJ, Goldberg AL and Maniatis T. The ubiquitin- proteasome pathway is required for processing the NFkB1 precursor protein and the activation of NF-kB. Cell 1994; 78: 773-785. #Goldberg AL, Gaczynska M, Grant E, Michalek M, Rock KL. Functions of the proteasome in antigen presentation. Cold Spring Harb Symp Quant Biol. 1995;60:479-90. PubMed PMID: 8824421. #Rock KL, Goldberg AL. Degradation of cell proteins and the generation of MHC class I-presented peptides. Annu Rev Immunol. 1999; 17: 739-79 #Goldberg AL. Development of proteasome inhibitors as research tools and cancer drugs. J Cell Biol. 2012 Nov 12;199(4):583-8. PubMed PMID: 23148232; PubMed Central PMCID: PMC3494858. #Coux O, Tanaka K, Goldberg AL. Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem. 1996;65:801-47. PubMed PMID: 8811196. #Smith DM, Chang SC, Park S, Finley D, Cheng Y, et al. Docking of the proteasomal ATPases' carboxyl termini in the 20S proteasome's alpha ring opens the gate for substrate entry. Mol Cell. 2007 Sep 7;27(5):731-44. PubMed PMID: 17803938; PubMed Central PMCID: PMC2083707. #Smith DM, Fraga H, Reis C, Kafri G, Goldberg AL. ATP binds to proteasomal ATPases in pairs with distinct functional effects, implying an ordered reaction cycle. Cell. 2011 Feb 18;144(4):526-38. PubMed PMID: 21335235; PubMed Central PMCID: PMC3063399. #Mitch WE, Goldberg AL. Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. N Engl J Med. 1996 Dec 19;335(25):1897-905. PubMed PMID: 8948566. #Lecker SH, Jagoe RT, Gilbert A, Gomes M, Baracos V, et al. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J. 2004 Jan;18(1):39-51. PubMed PMID: 14718385. #Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell. 2004 Apr 30;117(3):399-412. PubMed PMID: 15109499; PubMed Central PMCID: PMC3619734. #Cohen S, Nathan JA, Goldberg AL. Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov. 2015 Jan;14(1):58-74. PubMed PMID: 25549588. #Lokireddy, S, Kukushkin, NV, and Goldberg, AL. cAMP-induced phosphorylation of the 26S proteasome enhances its function and the degradation of misfolded proteins. Proc Natl Acad Sci USA. 2015 Dec 29; 112(52): E716-85. Doi 10.1073. PubMed PMID: 1522332112. #VerPlank J, Lokireddy S, Zhao J, Goldberg AL. 26S Proteasomes are rapidly activated by diverse hormones and physiological states that raise cAMP and cause Rpn6 phosphorylation. Proc Natl Acad Sci U S A. 2019. doi:10.1073/pnas.1809254116. PMID: 30782827. #VerPlank JJS, Tyrkalska SD, Fleming A, Rubinsztein DC, Goldberg AL. cGMP via PKG activates 26S proteasomes and enhances degradation of proteins, including ones that cause neurodegenerative diseases. Proc Natl Acad Sci U S A. 2020;117(25):14220-14230. doi:10.1073/pnas.2003277117. PMID: 32513741.

References

Harvard Medical School faculty Harvard College alumni Alumni of the University of Cambridge 1942 births Living people Members of the National Academy of Medicine {{improve categories, date=June 2021