Mcl-1L Cytoplasmic Domain (human, recombinant)

Myeloid cell leukemia-1 (Mcl-1) is a Bcl-2 family member protein that is involved in the regulation of apoptosis.¹ Alternative splicing of MCL1 pre-mRNA produces three isoforms, anti-apoptotic Mcl-1 long (Mcl-1L) and pro-apoptotic Mcl-1 short and Mcl-1 extra short (Mcl-1S and Mcl-1ES, respectively). Mcl-1L is composed of a C-terminal helix that acts as a membrane anchor, four Bcl-2 homology (BH) domains, and a PEST domain. The BH1, BH2, and BH3 domains facilitate heterodimerization with pro-apoptotic proteins, including Bax and Bak, and homodimerization with Mcl-1S and Mcl-1ES.^1,2,3 Mcl-1L is expressed during embryogenesis and hematopoiesis, as well as during nervous and immune system development, and localizes to the mitochondrial membrane.^4,5 It inhibits apoptosis by preventing Bax and Bak oligomerization, which form a pore on the outer mitochondrial membrane that allows release of cytochrome c into the cytoplasm.¹ Knockdown of MCL1 sensitizes oral cancer cells to cisplatin and tumor levels of Mcl-1L are increased relative to adjacent normal tissues in patients with oral cancer.⁶ Overexpression of MCL1 is associated with poor prognosis in several cancers, including solid tumors and hematological malignancies.¹ Cayman’s Mcl-1L Cytoplasmic Domain (human, recombinant) protein can be used for enzyme activity assays.

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1. Wang, H., Guo, M., Wei, H., et al. Targeting MCL-1 in cancer: Current status and perspectives. J. Hematol. Oncol. 14(1), 67 (2021).

2. Bae, J., Leo, C.P., Hsu, S.Y., et al. MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH₃ domain. The Journal of Biological Chemisty 275(33), 25255-25261 (2000).

3. Kim, J.-H., Sim, S.-H., Ha, H.-J., et al. MCL-1ES, a novel variant of MCL-1, associates with MCL-1L and induces mitochondrial cell death. FEBS Lett. 583(17), 2758-2764 (2009).

4. Opferman, J.T., and Kothari, A. Anti-apoptotic BCL-2 family members in development. Cell Death Differ. 25(1), 37-45 (2018).

5. Yang, T., Kozopas, K.M., and Craig, R.W. The intracellular distribution and pattern of expression of Mcl-1 overlap with, but are not identical to, those of Bcl-2. J. Cell Biol. 128(6), 1173-1184 (1995).

6. Palve, V., Mallick, S., Ghaisas, G., et al. Overexpression of Mcl-1L splice variant is associated with poor prognosis and chemoresistance in oral cancers. PLoS One 9(11), e111927 (2014).