induced myeloid leukemia cell differentiation protein Mcl-1; Bcl-2-related protein EAT/mcl1; mcl1/EAT; Bcl-2-like protein 3; Bcl2-L-3 (MCL1, BCL2L3)

Function

• role in regulation of apoptosis versus cell survival, & in maintenance of viability but not of proliferation
• mediates its effects by interactions with other regulators of apoptosis
• isoform 1 inhibits apoptosis
• isoform 2 promotes apoptosis
• cleaved by CASP3 during apoptosis
• in intact cells, cleavage occurs preferentially after Asp-127, yielding a pro-apoptotic 28 kD C-terminal fragment rapidly degraded in the absence of phosphorylation on Thr-163 in the PEST region
• phosphorylated on Thr-163
• treatment with taxol or okadaic acid induces phosphorylation on additional sites
• interacts with BAD, BOK, BIK & BFM (putative)
• interacts with PMAIP1
• isoform 1 interacts with BAX, BAK1, TPT1 & BCL2L11
• isoform 2 does not interact with pro-apoptotic BCL2-related proteins

Structure

• belongs to the Bcl-2 family
• heterodimer of isoform 1 & isoform 2
• homodimers of isoform 1 or isoform 2 are not detected

Compartment

• membrane, cytoplasm
• mitochondrion, nucleus, nucleoplasm
• cytoplasmic, associated with mitochondria

Alternative splicing

named isoforms=2

Expression

• expression increases early during phorbol-ester induced differentiation along the monocyte/macrophage pathway in myeloid leukemia cell lines ML-1
• rapidly up-regulated by CSF2 in ML-1 cells
• up-regulated by heat-shock induced differentiation
• expression increases early during retinoic acid-induced differentiation

Notes

• isolated from ML-1 human myeloid leukemia cell line during phorbol ester induced differentiation

More general terms

• PEST protein
• membrane protein
• bcl-2 subfamily protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4170
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4170
• OMIM: https://mirror.omim.org/entry/159552
• UniProt: http://www.uniprot.org/uniprot/Q07820.html