Induced myeloid leukemia cell differentiation protein Mcl-1 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 in humans is encoded by the ''MCL1''

gene 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 ...

Function

The protein encoded by this gene belongs to the

Bcl-2 family The Bcl-2 familyTC# 1.A.21 consists of a number of evolutionarily-conserved proteins that share Bcl-2 homology (BH) domains. The Bcl-2 family is most notable for their regulation of apoptosis, a form of programmed cell death, at the mitochondrion. ...

. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. The longer gene product (isoform 1) enhances cell survival by inhibiting

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

while the alternatively spliced shorter gene product (isoform 2) promotes apoptosis and is death-inducing. The protein MCL1 has a very short

biological half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of only 20–30 minutes. The loss of MCL1 has a more dramatic impact than the loss of any other anti-apoptotic member of the Bcl-2 family. Loss of the ''Mcl-1'' gene results in embryo death when the embryo is only around 3.5 days old, before it has even implanted. Conditional deletion of ''Mcl-1'' depletes a wide variety of cells, including

hematopoietic stem cell Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within t ...

s, B cell–committed progenitors, T cell–committed progenitors, antibody-secreting plasma cells,

cardiac muscle cell Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...

s, and

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

s. Deletion of ''Mcl-1'' in hepatocytes causes apoptosis and aberrant polyploidization but improves liver regeneration after surgery. MCL1 works synergistically with p53 in protecting liver from injury, fibrosis and cancer. MCL1 also has a role in the cell's energy production, working in the intermitochondrial space.

Clinical significance

Omacetaxine mepesuccinate Omacetaxine mepesuccinate (INN, trade names Synribo ), formerly named as homoharringtonine or HHT, is a pharmaceutical drug substance that is indicated for treatment of chronic myeloid leukemia (CML). HHT is a natural plant alkaloid derived from ...

(a drug approved for the treatment for

chronic myelogenous leukemia Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumulat ...

) and

Seliciclib Seliciclib (roscovitine or CYC202) is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors that preferentially inhibit multiple enzyme targets including CDK2, CDK7 and CDK9, which alter the growt ...

(which is under investigation as a potential

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 ...

treatment) both act in part by inhibiting synthesis of Mcl-1. MCL1 has been identified as a resistance factor for BCL-2 inhibitor venetoclax in lymphoma cells. Therefore, new strategies of combining BCL-2 and MCL1 inhibitors are currently under clinical trials for several tumor types.

Interactions

MCL1 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: * BAK1, *

BCL2L11 Bcl-2-like protein 11, commonly called BIM (Bcl-2 Interacting Mediator of cell death), is a protein that in humans is encoded by the ''BCL2L11'' gene. Function The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family ...

, * BID, *

BAD Bad or BAD may refer to: Common meanings *Evil, the opposite of moral good * Erroneous, inaccurate or incorrect * Unhealthy, or counter to well-being * Antagonist, the threat or obstacle of moral good Acronyms * BAD-2, a Soviet armored troll ...

, *

DAD1 Dolichyl-diphosphooligosaccharide—protein glycosyltransferase subunit DAD1 is an enzyme that in humans is encoded by the ''DAD1'' gene. Function DAD1, the defender against apoptotic cell death, was initially identified as a negative regulat ...

, * PMAIP1, *

PCNA Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication. PCNA is a homotrimer and achieves its processivity by encircling the DNA, whe ...

, *

TCTP Translationally Controlled Tumor Protein (TCTP) is a protein that in humans is encoded by the ''TPT1'' gene. The ''TPT1'' gene is mapped 13q12-q1413 in the Chromosome 13. The human gene contains five introns and six exons, The TPT1-gene contain ...

and *

TNKS Tankyrase, also known as tankyrase 1, is an enzyme that in humans is encoded by the ''TNKS'' gene. It inhibits the binding of TERF1 to telomeric DNA. Tankyrase attracts substantial interest in cancer research through its interaction with AXIN1 a ...

References

External links

* {{PDB Gallery, geneid=4170

Function

Clinical significance

Interactions

See also

References

Further reading

External links