Mcl-1 was first discovered in myeloid leukemia cells during differential screening of cDNA libraries31. Mcl-1 contains at least 3 putative Bcl-2 homology (BH) domains and experimentally can protect against apoptosis by interacting and sequestering proapoptotic Bcl-2 family member proteins (Fig. 8) including, Noxa (a BH3 only member of Bcl-2 family), PUMA (apoptosis regulator induced by p53), Bim (Bcl-2-like protein 11), and Bax protein (Bcl-2 associated X)32–34. Overexpression of Mcl-1 has been seen in various human tumors, including hematologic leukemia, ovarian cancer, prostate cancer, lung cancer, breast cancer, and pancreatic cancers35–38. Downregulation of Mcl-1 expression in tumor cells has been shown to increases the cancer cell sensitivity to drug treatments39,40, suggesting that Mcl-1 may play a critical role in cellular viability. Alternative splicing of Mcl-1 gene to form Mcl-1L and Mcl-1S isoforms is mainly regulated by SRSF124,41 (Fig. 8). The shorter isoform Mcl-1S lacks BH1 and BH2 domains due to the exclusion of exon 2 during splicing. While Mcl-1L could enhance cell survival, the alternatively spliced Mcl-1S was shown to be associated with apoptosis induction26,42. In addition to its role in
