Understanding MCL1: from cellular function and regulation to pharmacological inhibition

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 contribu...

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Bibliographic Details
Published in:The FEBS journal 2022-10, Vol.289 (20), p.6209-6234
Main Authors: Sancho, Mónica, Leiva, Diego, Lucendo, Estefanía, Orzáez, Mar
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Apoptosis
BCL2 family
Cancer
Cell cycle
Cell Death
Cell Line, Tumor
Cell Survival
Chemotherapy
Homeostasis
Inhibitors
Leukemia
Mcl-1 protein
MCL1
MCL1 inhibitor
Mitochondria
Myeloid Cell Leukemia Sequence 1 Protein - genetics
Myeloid Cell Leukemia Sequence 1 Protein - metabolism
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - metabolism
State‐of‐the‐Art Review
State‐of‐the‐Art Reviews
Structure-function relationships
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Summary: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. Myeloid cell leukemia‐1 (MCL1) is an antiapoptotic member of the BCL2 family whose dysregulation contributes to cell survival and resistance to diverse chemotherapeutic agents. This review summarizes the current knowledge regarding the complexity of MCL1 regulation, structure, and function that could influence the clinical success of MCL1 inhibitors.
ISSN:1742-464X
1742-4658
DOI:10.1111/febs.16136