Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ejcb.2017.09.002
Title: BH3-only protein BIM: An emerging target in chemotherapy
Authors: Shukla, Shatrunajay
Saxena, Sugandh
Singh, Brijesh Kumar 
Kakkar, Poonam
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Bcl-2 family
Bim
Mitochondria
Apoptosis
Cell signalling
Cancer
CHRONIC LYMPHOCYTIC-LEUKEMIA
HISTONE DEACETYLASE INHIBITOR
STRESS-INDUCED APOPTOSIS
STRUCTURE-GUIDED DESIGN
BCL-2 FAMILY PROTEINS
RANDOMIZED PHASE-II
CELL-CYCLE ARREST
HIGH-AFFINITY
UP-REGULATION
TRANSCRIPTIONAL REGULATION
Issue Date: 1-Dec-2017
Publisher: ELSEVIER GMBH
Citation: Shukla, Shatrunajay, Saxena, Sugandh, Singh, Brijesh Kumar, Kakkar, Poonam (2017-12-01). BH3-only protein BIM: An emerging target in chemotherapy. EUROPEAN JOURNAL OF CELL BIOLOGY 96 (8) : 728-738. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ejcb.2017.09.002
Abstract: BH3-only proteins constitute major proportion of pro-apoptotic members of B-cell lymphoma 2 (Bcl-2) family of apoptotic regulatory proteins and participate in embryonic development, tissue homeostasis and immunity. Absence of BH3-only proteins contributes to autoimmune disorders and tumorigenesis. Bim (Bcl-2 Interacting Mediator of cell death), most important member of BH3-only proteins, shares a BH3-only domain (9–16 aa) among 4 domains (BH1-BH4) of Bcl-2 family proteins and highly pro-apoptotic in nature. Bim initiates the intrinsic apoptotic pathway under both physiological and patho-physiological conditions. Reduction in Bim expression was found to be associated with tumor promotion and autoimmunity, while overexpression inhibited tumor growth and drug resistance as cancer cells suppress Bim expression and stability. Apart from its role in normal homeostasis, Bim has emerged as a central player in regulation of tumorigenesis, therefore gaining attention as a plausible target for chemotherapy. Regulation of Bim expression and stability is complicated and regulated at multiple levels viz. transcriptional, post-transcriptional, post-translational (preferably by phosphorylation and ubiquitination), epigenetic (by promoter acetylation or methylation) including miRNAs. Furthermore, control over Bim expression and stability may be exploited to enhance chemotherapeutic efficacy, overcome drug resistance and select anticancer drug regimen as various chemotherapeutic agents exploit Bim as an executioner of cell death. Owing to its potent anti-tumorigenic activity many BH3 mimetics e.g. ABT-737, ABT-263, obatoclax, AT-101and A-1210477 have been developed and entered in clinical trials. It is more likely that in near future strategies commanding Bim expression and stability ultimately lead to Bim based therapeutic regimen for cancer treatment.
Source Title: EUROPEAN JOURNAL OF CELL BIOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/226755
ISSN: 01719335
16181298
DOI: 10.1016/j.ejcb.2017.09.002
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