Protein inhibitor of activated STAT (PIAS), also known as E3 SUMO-protein ligase PIAS, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that regulates transcription in

mammals Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

. PIAS proteins act as transcriptional co-regulators with at least 60 different proteins in order to either activate or repress

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 ...

. The

transcription factors 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 func ...

STAT STAT, Stat. , or stat may refer to: * Stat (system call), a Unix system call that returns file attributes of an inode * ''Stat'' (TV series), an American sitcom that aired in 1991 * Stat (website), a health-oriented news website * STAT protein, a ...

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...

p73 p73 is a protein related to the p53 tumor protein. Because of its structural resemblance to p53, it has also been considered a tumor suppressor. It is involved in cell cycle regulation, and induction of apoptosis. Like p53, p73 is characterized ...

, and

p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

are among the many proteins that PIAS interacts with. The seven proteins that belong to the mammalian PIAS

family Family (from la, familia) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its ...

are encoded by four

genes In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

: ''

PIAS1 E3 SUMO-protein ligase PIAS1 is an enzyme that in humans is encoded by the ''PIAS1'' gene. Function This gene encodes a member of the mammalian PIAS rotein inhibitor of activated STAT-1 (signal transducer and activator of transcription-1)famil ...

'', ''

PIAS2 E3 SUMO-protein ligase PIAS2 is an enzyme that in humans is encoded by the ''PIAS2'' gene. Interactions Protein inhibitor of activated STAT2 has been shown to interact with: * Androgen receptor, * DNMT3A, * PARK7, and * UBE2I SUMO-conjugat ...

'' (''PIASx''), ''

PIAS3 E3 SUMO-protein ligase PIAS3 is an enzyme that in humans is encoded by the PIAS3 gene. PIAS family The mammalian PIAS family consists of four members: PIAS1, PIAS2, PIAS3 and PIAS4. In Drosophila, a single PIAS homologue named dPIAS/Zimp has be ...

'', and ''

PIAS4 E3 SUMO-protein ligase PIAS4 is one of several protein inhibitor of activated STAT (PIAS) proteins. It is also known as protein inhibitor of activated STAT protein gamma (PIASg or PIASy), and is an enzyme that in humans is encoded by the ''PIAS4' ...

'' (''PIASy''). Apart from PIAS1, each gene encodes two protein

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

. Homologues of PIAS proteins have been found in other

eukaryotes Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

, including Zimp/dPIAS in ''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly" or "pomace fly". Starting with Ch ...

'' and zfPIAS4a in

zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family ( Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...

. SIZ1 and SIZ2 were two homologues identified in

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...

. PIAS proteins contain each conserved

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined **Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function * Do ...

and motif of the PIAS protein family, with a few exceptions. The known functions of these domains and motifs are similar among all PIAS protein family members. These functions include acting as E3

SUMO is a form of competitive full-contact wrestling where a ''rikishi'' (wrestler) attempts to force his opponent out of a circular ring (''dohyō'') or into touching the ground with any body part other than the soles of his feet (usually by thr ...

-protein

ligase In biochemistry, a ligase is an enzyme that can catalyze the joining (ligation) of two large molecules by forming a new chemical bond. This is typically via hydrolysis of a small pendant chemical group on one of the larger molecules or the enzym ...

s during SUMOylation, which is an important process in transcriptional regulation. Presently, less is known about the higher order

structure A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

of PIAS proteins. The three-dimensional protein structures of PIAS2, PIAS3, and SIZ1 have only recently been solved. PIAS proteins have potential applications in cancer treatment and prevention. They may also play an important role in regulating

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 ...

responses.

Discovery

The discovery of PIAS3 was first published in 1997. The discovery was made while the JAK-STAT pathway was being studied. The discovery of other PIAS proteins, including PIAS1, PIASxα, PIASxβ, and PIASy, was published the following year. The interaction between STATs and PIASs was characterized by the yeast two-hybrid assay. PIAS proteins were named based on their ability to inhibit STAT. For example, PIAS1 inhibited STAT1, and PIAS3 inhibited STAT3. When it was discovered that PIAS proteins did far more than simply inhibit STATs, it was proposed that the PIAS acronym should stand for Pleiotropic Interactors Associated with SUMO based on their association with SUMO proteins. Additionally, E3 SUMO-protein ligase PIAS is an alternative name for PIAS proteins. The discovery of PIAS3L, an isoform of PIAS3, was published in 2003. In addition, the discovery of PIASyE6- was published in 2004. It is an isoform of PIASy that doesn't contain exon 6.

Types of PIAS proteins

The table below lists the seven known proteins that belong to the mammalian PIAS protein family. Due to

alternative splicing Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...

, some PIAS protein-encoding genes encode multiple protein products called isoforms. ''PIAS1'' is the only gene of this family that does not encode any isoforms.

Homologues

Homologues of PIAS proteins have been found in other eukaryotes, and several are listed below: *Zimp/dPIAS in ''

'' *zfPIAS4a in

*SIZ1 and SIZ2 in

Function

PIAS proteins contribute to the control of gene expression, and may be considered transcriptional co-regulators. While PIAS proteins interact with at least 60 different proteins involved in transcription, they are known to act as E3 SUMO-protein ligases. In essence, the RING-finger-like zinc-binding domain of the PIAS protein assists in the attachment of a SUMO protein to the target

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 ...

. Attachment of a SUMO protein to the target allows for

protein–protein interaction Protein–protein interactions (PPIs) are physical contacts of high specificity established between two or more protein molecules as a result of biochemical events steered by interactions that include electrostatic forces, hydrogen bonding and th ...

between PIAS and the transcription factor. This interaction can either upregulate or downregulate transcription. For example, the activity of transcription factor

was stimulated after it was SUMOylated by PIASy. In contrast, the activity of transcription factor

was repressed after it was SUMOylated by PIAS1. One function of PIAS proteins is to relocate transcriptional regulators to different compartments within the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom * Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...

of the

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 ...

. PIAS proteins also play a key role in double-stranded break

DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...

. Exposure to

UV light Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...

chemicals A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., wit ...

, and

ionizing radiation Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel ...

can cause DNA damage, and the most detrimental type of DNA damage is a double-stranded break. PIAS1, PIAS3, and PIAS4 have been shown to recruit proteins to the site of the damage and promote repair. Additionally, PIAS proteins are important transcriptional co-regulators of the JAK/STAT signaling pathway. PIAS protein's interaction with STAT signaling requires

tyrosine phosphorylation Tyrosine phosphorylation is the addition of a phosphate (PO43−) group to the amino acid tyrosine on a protein. It is one of the main types of protein phosphorylation. This transfer is made possible through enzymes called tyrosine kinases. Tyros ...

of STAT proteins. Additionally, PIAS1 binds preferentially to un-

methylated In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These ...

STAT1 Signal transducer and activator of transcription 1 (STAT1) is a transcription factor which in humans is encoded by the ''STAT1'' gene. It is a member of the STAT protein family. Function All STAT molecules are phosphorylated by receptor associ ...

. Although the exact mechanism isn't clear, PIAS1 and PIASy both inhibit STAT1 signaling. PIAS3 was found to specifically inhibit

STAT3 Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the ''STAT3'' gene. It is a member of the STAT protein family. Function STAT3 is a member of the STAT protein family. In respons ...

signaling after stimulation by the

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

IL-6. Also, it is known that PIAS1 can inhibit

activity upon stimulation by the cytokine

TNF Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

and the LPS endotoxin.

Structure

The three-dimensional

protein structure Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, the monomers of the polymer. A single amino acid monomer ma ...

s of PIAS2, PIAS3, and PIAS-like protein SIZ1 were recently solved using

X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...

. The structures of PIAS2 and PIAS3 were listed in the

Structural Genomics Consortium The Structural Genomics Consortium (SGC) is a public-private-partnership focusing on elucidating the functions and disease relevance of all proteins encoded by the human genome, with an emphasis on those that are relatively understudied. The SGC pl ...

in 2012 and 2013, respectively, by A. Dong et al. Details of the SIZ1 structure were published by Ali A. Yunus and Christopher D. Lima in 2009. Four PIAS domains and two PIAS motifs have been identified. They include the

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

scaffold attachment factor-A/B, acinus and PIAS (SAP) domain, the

Pro Pro is an abbreviation meaning "professional". Pro, PRO or variants thereof may also refer to: People * Miguel Pro (1891–1927), Mexican priest * Pro Hart (1928–2006), Australian painter * Mlungisi Mdluli (born 1980), South African retired f ...

Ile Ile may refer to: * iLe, a Puerto Rican singer * Ile District (disambiguation), multiple places * Ilé-Ifẹ̀, an ancient Yoruba city in south-western Nigeria * Interlingue (ISO 639:ile), a planned language * Isoleucine, an amino acid * Anothe ...

- Asn-Ile- Thr (PINIT) motif, the

RING Ring may refer to: * Ring (jewellery), a round band, usually made of metal, worn as ornamental jewelry * To make a sound with a bell, and the sound made by a bell :(hence) to initiate a telephone connection Arts, entertainment and media Film and ...

finger A finger is a limb of the body and a type of digit, an organ of manipulation and sensation found in the hands of most of the Tetrapods, so also with humans and other primates. Most land vertebrates have five fingers ( Pentadactyly). Chambers ...

-like

zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...

-binding domain (RLD), the highly acidic domain (AD), the SUMO-interacting motif (SIM), and the

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO� ...

-rich C-terminal region (S/T).

SAP

The N-terminal scaffold attachment factor-A/B, acinus and PIAS (SAP) domain is found in all PIAS proteins. It is composed of four

alpha helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ear ...

. It binds to areas of

chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...

that are rich in

adenine Adenine () ( symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its derivati ...

(A) and

thymine Thymine () ( symbol T or Thy) is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nu ...

(T). These A/T rich regions are known as matrix-attachment regions. Once bound, the matrix-attachment regions anchor loops of chromatin to the

nuclear matrix In biology, the nuclear matrix is the network of fibres found throughout the inside of a cell nucleus after a specific method of chemical extraction. According to some it is somewhat analogous to the cell cytoskeleton. In contrast to the cytoskelet ...

. The nuclear matrix is a structure within the nucleus where it is thought that transcription regulation takes place. SAP also binds to p53. Each SAP domain contains an LXXLL amino acid motif. L =

leucine Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- ca ...

, and X = any amino acid. This motif is used to bind to

nuclear receptors In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of specif ...

. Nuclear receptors are

that regulate transcription upon

ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...

binding.

PINIT

The Pro-Ile-Asn-Ile-Thr (PINIT) motif was discovered in PIAS3L, an isoform of PIAS3. PIAS proteins tend to go back and forth between the

and

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

as they carry out their activities. PINIT is needed to localize PIAS3 and PIAS3L to the nucleus. PIASy has a slight difference in its PINIT motif:

is in place of the second isoleucine (PINLT). Furthermore, the PINIT motif is not found in PIASy isoform PIASyE6-. This isoform, lacking exon 6, is still retained in the nucleus despite lacking the PINIT motif. The reason for this is unknown.

RLD

The RING-finger-like zinc-binding domain is present in all PIAS proteins. RLD is essential for PIAS proteins to function as E3 SUMO-protein ligases. It is also needed for successful interaction with other proteins. Its three dimensional structure is thought to be similar to typical

finger domains. It contains one

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...

residue and five

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

residues

AD and SIM

The highly acidic domain (AD), present in all PIAS proteins, contains a SUMO-interacting motif (SIM). The SIM motif may be needed for PIAS proteins to accurately recognize and interact with other SUMO proteins. However, it is not needed for E3 SUMO-protein ligase activity to occur. The function of the highly acidic domain is unknown.

S/T

The Serine/threonine-rich C-terminal (S/T) region is not found in all PIAS proteins. PIASy and PIASyE6- are the only members of the PIAS protein family that lack this region. Furthermore, the length of this region varies among PIAS protein isoforms. The function of the S/T region is unknown.

Potential applications

Defects in the

system lead to a predisposition for developing cancer. At least some of the PIAS proteins are implicated in DNA repair, and specifically in enhancing repair of double-stranded breaks. In cell culture, overexpression of PIAS3 demonstrated an increased resistance of

HeLa HeLa (; also Hela or hela) is an immortalized cell line used in scientific research. It is the oldest and most commonly used human cell line. The line is derived from cervical cancer cells taken on February 8, 1951, named after Henrietta La ...

cells to

. This indicates a significant role for PIAS3 in DNA repair. Additionally, overexpression of PIAS3 inhibited human lung cancer cell growth in vitro and rendered cancer cells up to twelve times more sensitive to

chemotherapeutic Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothera ...

drugs. While inhibition of PIAS by siRNAs led cancer cells to accelerate cell proliferation and demonstrate higher levels of resistance to chemotherapy drugs. In a study of human brain tissue samples from

glioblastoma multiforme Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...

patients, PIAS3 expression was found to be reduced compared to the control brain tissue. Inhibition of PIAS3 resulted in increased glioblastoma propagation, while PIAS3 overexpression inhibited STAT-3 signaling and cell proliferation . Furthermore, patients with higher levels of

BRCA1 Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a h ...

, PIAS1, and PIAS4 survived for a longer period of time in a retrospective study of advanced

gastric cancer Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymph ...

patients. Continuous activation of the JAK-STAT pathway can cause cancer in humans as well as less complex organisms such as

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...

. Given the preliminary evidence and their effects on important signaling pathways involved in cancer, PIAS proteins may be interesting targets for the development of treatments for cancers or as sensitizers for chemotherapeutic drugs and radiation in BRCA-deficient cancers. In addition to its importance in various cancers, the JAK-STAT signaling pathway plays an important part in the human immune response and in particular with regards to

adaptive immunity The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...

. Clinical proof of concept for the use of JAK inhibitors for treatment of autoimmune and inflammatory disease has been demonstrated by Pfizer's

tofacitinib Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. Common side effects include diarrhea, headache, and high blood pressure. Serious side eff ...

, a JAK inhibitor recently approved in the US for the treatment of

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...

. Additionally, tofacitinib is currently being studied for the treatment of

ankylosing spondylitis Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine typically where the spine joins the pelvis. Occasionally areas affected may include other joints such as the shoulders or hip ...

psoriatic arthritis Psoriatic arthritis is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. Th ...

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...

atopic dermatitis Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (dermatitis). It results in puritis, itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which often thickens o ...

, and

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...

. Furthermore,

and STAT2 are essential factors in the cellular antiviral and adaptive immune defenses. PIAS proteins and other regulators are necessary for homeostasis and for fine tuning the immune response. PIAS proteins regulate STAT transcription through several mechanisms, and genetic studies in rodents have shown that PIAS1 plays an important physiological role in STAT1 regulation. Many of the 60 proteins that PIAS protein family is believed to interact with are immune regulatory factors.

References

External links

PIAS protein entry
at the

Protein Information Resource The Protein Information Resource (PIR), located at Georgetown University Medical Center, is an integrated public bioinformatics resource to support genomic and proteomic research, and scientific studies. It contains protein sequences databases Hi ...

(PIR) * {{JAK-STAT signaling pathway Proteins Cell signaling