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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''MCL1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Function

The protein encoded by this gene belongs to the

Bcl-2 family The Bcl-2 family (TC# 1.A.21) consists of a number of Conserved sequence, evolutionarily-conserved proteins that share Bcl-2 Sequence homology, homology (BH) domains. The Bcl-2 family is most notable for their regulation of apoptosis, a form of pro ...

. 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 ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

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 (elimination half-life, pharmacological half-life) is the time taken for concentration of a drug, biological substance (such as a medication) to decrease from its maximum concentration (chemistry), concentration (Cmax (pharm ...

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 first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the ...

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

cardiac muscle cell Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the Heart#Wa ...

s, and

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

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 (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 accumula ...

) and Seliciclib (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 antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...

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 promiscuously interact 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 In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredit ...

, commonly called BIM, * 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 trolley ...

, * DAD1, * PMAIP1, commonly called NOXA, *

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

, * PUMA, * TCTP 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