靶点背景MCL1 (Myeloid cell leukemia-1) belongs to the Bcl-2 family and is involved in programing, differentiation and concomitant maintenance of cell viability, but not of proliferation. Isoform 1 of MCL1 inhibits apoptosis while isoform 2 promotes it. The carboxy terminal of MCL1 and bcl-2 share significant sequence homology. Expression of MCL1 is increased upon exposure of ML-1 cells to various types of DNA damaging agents (e.g. ionizing radiation, ultraviolet radiation, and alkylating drugs) along with increases in GADD45 and Bax and a decrease in bcl-2. Enhanced expression of MCL1, prominently associated with mitochondria, complements the continued expression of bcl-2 in ML-1 cells undergoing differentiation. Like bcl-2, MCL1 has the capacity to promote cell viability under conditions that otherwise cause apoptosis. While the mechanism by which MCL1 inhibits apoptosis is not known, it is thought that it may heterodimerize and neutralize pro-apoptotic members of the Bcl-2 family such as Bim or Bak. MCL1 was originally identified in differentiating myeloid cells, but has since been shown to be expressed in multiple cell types. MCL1 is essential for embryogenesis and for the development and maintenance of B and T lymphocytes in animals. MCL1 exists as at least two distinct isoforms designated MCL1L and MCL1S. In marked contrast to the larger isoform of MCL1, overexpression of MCL1S promotes cell death.
