Understanding MCL1: from cellular function and regulation to pharmacological inhibition

Related Experiment Video

Updated: Oct 26, 2025

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

7.6K

Mónica Sancho1, Diego Leiva1, Estefanía Lucendo1

  • 1Targeted Therapies on Cancer and Inflammation Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain.

The FEBS Journal
|July 26, 2021
PubMed

Insights

Myeloid cell leukemia-1 (MCL1) is crucial for cancer cell survival and drug resistance. Understanding MCL1

Area of Science:

  • Molecular biology
  • Cancer research
  • Cell death regulation

Background:

  • Myeloid cell leukemia-1 (MCL1) is an antiapoptotic protein in the BCL2 family.
  • MCL1 has a short half-life, acting as a rapid regulator of cell death, cell cycle, and mitochondrial homeostasis.
  • Overexpression of MCL1 in cancer promotes cell survival and resistance to chemotherapy.

Purpose of the Study:

  • To summarize current knowledge on MCL1 structure, regulation, and function.
  • To analyze how these factors impact the therapeutic potential of MCL1 inhibitors.
  • To address challenges in the clinical application of MCL1 inhibitors.

Main Methods:

  • Literature review of existing research on MCL1.
  • Analysis of MCL1's role in apoptosis and non-apoptotic functions.
  • Evaluation of preclinical and clinical data for MCL1 inhibitors.

Main Results:

  • MCL1's antiapoptotic role is well-established, contributing to cancer survival.
  • Non-apoptotic functions of MCL1 may affect the efficacy of inhibitors.
  • Complex regulation of MCL1 presents challenges for targeted therapies.

Conclusions:

  • Further understanding of MCL1's multifaceted roles is essential for successful cancer treatment.
  • Targeting MCL1 requires consideration of both its apoptotic and non-apoptotic functions.
  • Overcoming challenges in MCL1 inhibition is key to improving cancer therapy outcomes.
Keywords:
BCL2 familyMCL1MCL1 inhibitorapoptosiscell cycle

More Related Videos

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

13.4K
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.4K

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.4K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.2K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.1K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.8K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.2K