Induced myeloid leukaemia cell differentiation protein Mcl-1 (Mcl-1)

Induced myeloid leukaemia cell differentiation protein Mcl-1 is a short-lived, anti-apoptotic member of the Bcl-2 family, encoded by the MCL1 gene in humans[1][3]. Mcl-1 functions by binding and neutralizing pro-apoptotic molecules such as Bak and Bax via its BH3-binding groove, thereby inhibiting mitochondrial outer membrane permeabilization and apoptosis[1][2][3]. It plays a fundamental role in the development and survival of hematopoietic cells, cardiac myocytes, neurons, and other cell types. Amplification and overexpression of MCL1 are common in many human cancers, contributing to chemotherapy resistance and tumor cell survival[2][3]. Drugs targeting Mcl-1 operate by BH3-mimetic mechanisms, aiming to induce apoptosis selectively in cancer cells overexpressing Mcl-1[2][3]. However, clinical application is challenged by the essential physiological roles of Mcl-1 in healthy tissues and the risk of toxicity. Mcl-1 levels and gene status are considered useful biomarkers for patient selection in clinical trials of Mcl-1 inhibitors[2][3].

Other names

Myeloid cell leukemia-1MCL1BCL2 family apoptosis regulator MCL1MCL1 apoptosis regulator, BCL2 family member

BH3-mimetic inhibition (mimics BH3-only proteins, blocks Mcl-1’s anti-apoptotic function); Induction of apoptosis in cancer cells by preventing Mcl-1 from sequestering pro-apoptotic proteins (Bak, Bax)