Phospho-MCL1 (Thr163)

This gene encodes an anti-apoptotic protein, which is a member of the Bcl-2 family. Alternative splicing results in multiple transcript variants. The longest gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene products (isoform 2 and isoform 3) promote apoptosis and are death-inducing. [provided by RefSeq, Oct 2010]

Full Name

MCL1, BCL2 Family Apoptosis Regulator

Function

Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.

Biological Process

Cell fate determination Source: UniProtKB
Cellular homeostasis Source: UniProtKB
Extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damage Source: GO_Central
Negative regulation of anoikis Source: UniProtKB
Negative regulation of apoptotic process Source: BHF-UCL
Negative regulation of autophagy Source: UniProtKB
Negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
Negative regulation of intrinsic apoptotic signaling pathway Source: GO_Central
Positive regulation of apoptotic process Source: ComplexPortal
Positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
Regulation of apoptotic process Source: ComplexPortal
Regulation of response to DNA damage stimulus Source: MGI
Response to cytokine Source: MGI

Cellular Location

Mitochondrion
Cytoplasm
Nucleus
nucleoplasm
Other locations
Membrane
Note: Cytoplasmic, associated with mitochondria.

Topology

Helical: 328-348

PTM

Cleaved by CASP3 during apoptosis. In intact cells cleavage occurs preferentially after Asp-127, yielding a pro-apoptotic 28 kDa C-terminal fragment.
Rapidly degraded in the absence of phosphorylation on Thr-163 in the PEST region.
Phosphorylated on Ser-159, by GSK3, in response to IL3/interleukin-3 withdrawal. Phosphorylation at Ser-159 induces ubiquitination and proteasomal degradation, abrogating the anti-apoptotic activity. Treatment with taxol or okadaic acid induces phosphorylation on additional sites.
Ubiquitinated. Ubiquitination is induced by phosphorylation at Ser-159.