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Understanding MCL1: from cellular function and regulation to pharmacological inhibition
Author(s) -
Sancho Mónica,
Leiva Diego,
Lucendo Estefanía,
Orzáez Mar
Publication year - 2022
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.16136
Subject(s) - mcl1 , function (biology) , cancer , cancer research , biology , medicine , bioinformatics , computational biology , pharmacology , neuroscience , microbiology and biotechnology , downregulation and upregulation , gene , genetics
Myeloid cell leukemia‐1 (MCL1), an antiapoptotic member of the BCL2 family characterized by a short half‐life, functions as a rapid sensor that regulates cell death and other relevant processes that include cell cycle progression and mitochondrial homeostasis. In cancer, MCL1 overexpression contributes to cell survival and resistance to diverse chemotherapeutic agents; for this reason, several MCL1 inhibitors are currently under preclinical and clinical development for cancer treatment. However, the nonapoptotic functions of MCL1 may influence their therapeutic potential. Overall, the complexity of MCL1 regulation and function represent challenges to the clinical application of MCL1 inhibitors. We now summarize the current knowledge regarding MCL1 structure, regulation, and function that could impact the clinical success of MCL1 inhibitors.