BCL2A1: the underdog in the BCL2 family

Cell Death Differ. 2012 Jan;19(1):67-74. doi: 10.1038/cdd.2011.158. Epub 2011 Nov 11.


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.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Apoptosis*
  • Gene Expression Regulation
  • Humans
  • Mice
  • Minor Histocompatibility Antigens
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Protein Binding
  • Protein Conformation
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*


  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • BCL2-related protein A1
  • Minor Histocompatibility Antigens
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2