Understanding MCL1: from cellular function and regulation to pharmacological inhibition

Autores de CIPF

• 

  Mónica Sancho Medina

  Autor

• Diego Leiva Yuste

  Autor

• Estefanía Lucendo Gutiérrez

  Autor

• 

  Maria Mar Orzáez Calatayud

  Autor

Grupos de Investigación

• Laboratorio de Terapias Dirigidas en Cáncer e Inflamación

  

  Jefe/a de Grupo

  Maria Mar Orzáez Calatayud

Abstract

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.

Keywords

• apoptosis; BCL2 family; cell cycle; MCL1; MCL1 inhibitor