Myeloid cell leukemia 1 apoptosis regulator, Bcl-2 family member (MCL1)

Myeloid cell leukemia 1 (MCL1) is an anti-apoptotic intracellular protein that is part of the Bcl-2 family of apoptosis regulators[1][2][3]. It is a key determinant of cell survival by preventing apoptosis through direct interaction with pro-apoptotic Bcl-2 family members, particularly BAK and BAX, at the outer mitochondrial membrane[1][3]. MCL1 is unique among Bcl-2 proteins for its rapid turnover and its regulation at multiple cellular levels, including transcription, mRNA stability, and post-translational modifications (notably through its long, unstructured N-terminus)[3]. In addition to suppressing cell death, MCL1 controls mitochondrial dynamics (fusion/fission)[1][3][5], modulates DNA damage repair, regulates autophagy and mitophagy, and influences cell cycle progression[1][3]. Because of its critical role in cell proliferation and death, MCL1 is an important therapeutic target in cancer, particularly in tumors driven by anti-apoptotic mechanisms or resistance to chemotherapy[3]. Pharmacological inhibition of MCL1 releases the apoptotic block, leading to cancer cell death, but safety concerns remain due to MCL1’s essential functions in normal tissue, especially the heart and hematopoietic compartment[3]. Elevated MCL1 is associated with poor prognosis and resistance to targeted therapies.

Other names

Induced myeloid leukemia cell differentiation protein Mcl-1BCL2L3Bcl2-L-3Bcl-2-like protein 3Bcl-2-related protein EAT/mcl1EATMCL1-ESMCL1LMCL1SMyeloid cell leukemia 1C1orf138mcl1/EATADAMTSL4-AS1TMMyeloid cell leukemia sequence 1 (BCL2-related)

Inhibition of anti-apoptotic function (BH3 mimetics) by disrupting MCL1-protein interaction (e.g., BAK/BAX) to induce apoptosis. This can lead to destabilization of the mitochondrial network and ultimately cell death. It can also induce cell cycle arrest and DNA damage.