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BCL2A1: the underdog in the BCL2 family

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  • PMID: 22075983
  • PMCID: PMC3252829
  • DOI: 10.1038/cdd.2011.158

Free PMC article

BCL2A1: the underdog in the BCL2 family

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Author

Affiliation

  • PMID: 22075983
  • PMCID: PMC3252829
  • DOI: 10.1038/cdd.2011.158

Abstract

B-cell lymphoma 2 (BCL2) proteins are important cell death regulators, whose main function is to control the release of cytochrome c from mitochondria in the intrinsic apoptotic pathway. They comprise both pro- and anti-apoptotic proteins, which interact in various ways to induce or prevent pore formation in the outer mitochondrial membrane. Due to their central function in the apoptotic machinery, BCL2 proteins are often deregulated in cancer. To this end, many anti-apoptotic BCL2 proteins have been identified as important cellular oncogenes and attractive targets for anti-cancer therapy. In this review, the existing knowledge on B-cell lymphoma 2-related protein A1 (BCL2A1)/Bcl-2-related gene expressed in fetal liver (Bfl-1), one of the less extensively studied anti-apoptotic BCL2 proteins, is summarized. BCL2A1 is a highly regulated nuclear factor κB (NF-κB) target gene that exerts important pro-survival functions. In a physiological context, BCL2A1 is mainly expressed in the hematopoietic system, where it facilitates survival of selected leukocytes subsets and inflammation. However, BCL2A1 is overexpressed in a variety of cancer cells, including hematological malignancies and solid tumors, and may contribute to tumor progression. Therefore, the development of small molecule inhibitors of BCL2A1 may be a promising approach mainly to sensitize tumor cells for apoptosis and thus improve the efficiency of anti-cancer therapy.

Figures

Protein sequence alignment of human…

Protein sequence alignment of human and mouse BCL2A1. Besides full-length human BCL2A1 (Q16548),…

Structure of BCL2A1 in complex…

Structure of BCL2A1 in complex with BH3 peptides. Binding of human BCL2A1 (in…

Interaction partners of BCL2A1. Binding…

Interaction partners of BCL2A1. Binding by BCL2A1 can inhibit or neutralize pro-apoptotic multidomain…

Regulation of BCL2A1. BCL2A1 transcription…

Regulation of BCL2A1. BCL2A1 transcription is induced by NF- κ B, retinoic X…

B-cell lymphoma 2 (BCL2) proteins are important cell death regulators, whose main function is to control the release of cytochrome c from mitochondria in the intrinsic apoptotic pathway. They comprise both pro- and anti-apoptotic proteins, which interact in various ways to induce or prevent pore for …

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Underdog Genetics

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Underdog Genetics

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