Cancer cell death strategies by targeting Bcl-2's BH4 domain.


Journal

Biochimica et biophysica acta. Molecular cell research
ISSN: 1879-2596
Titre abrégé: Biochim Biophys Acta Mol Cell Res
Pays: Netherlands
ID NLM: 101731731

Informations de publication

Date de publication:
04 2021
Historique:
received: 18 12 2020
revised: 19 01 2021
accepted: 20 01 2021
pubmed: 8 2 2021
medline: 18 9 2021
entrez: 7 2 2021
Statut: ppublish

Résumé

The Bcl-2-family proteins have long been known for their role as key regulators of apoptosis. Overexpression of various members of the family is associated with oncogenesis. Its founding member, anti-apoptotic Bcl-2 regulates cell death at different levels, whereby Bcl-2 emerged as a major drug target to eradicate cancers through cell death. This resulted in the development of venetoclax, a Bcl-2 antagonist that acts as a BH3 mimetic. Venetoclax already entered the clinic to treat relapse chronic lymphocytic leukemia patients. Here, we discuss the role of Bcl-2 as a decision-maker in cell death with focus on the recent advances in anti-cancer therapeutics that target the BH4 domain of Bcl-2, thereby interfering with non-canonical functions of Bcl-2 in Ca

Identifiants

pubmed: 33549704
pii: S0167-4889(21)00037-9
doi: 10.1016/j.bbamcr.2021.118983
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
BCL2 protein, human 0
BIRD-2 peptide 0
Peptides 0
Proto-Oncogene Proteins c-bcl-2 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

118983

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

Auteurs

Ian de Ridder (I)

KU Leuven, Lab. Molecular & Cellular Signaling, Dep. Cellular & Molecular Medicine, Campus Gasthuisberg O/N-I bus 802, Herestraat 49, BE-3000 Leuven, Belgium.

Martijn Kerkhofs (M)

KU Leuven, Lab. Molecular & Cellular Signaling, Dep. Cellular & Molecular Medicine, Campus Gasthuisberg O/N-I bus 802, Herestraat 49, BE-3000 Leuven, Belgium.

Santhini Pulikkal Veettil (SP)

KU Leuven, Molecular Design and Synthesis, Department of Chemistry, Celestijnenlaan 200F, B-3001 Leuven, Belgium.

Wim Dehaen (W)

KU Leuven, Molecular Design and Synthesis, Department of Chemistry, Celestijnenlaan 200F, B-3001 Leuven, Belgium.

Geert Bultynck (G)

KU Leuven, Lab. Molecular & Cellular Signaling, Dep. Cellular & Molecular Medicine, Campus Gasthuisberg O/N-I bus 802, Herestraat 49, BE-3000 Leuven, Belgium. Electronic address: geert.bultynck@kuleuven.be.

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Classifications MeSH