BCL2A1: the underdog in the BCL2 family

被引:249
作者
Vogler, M. [1 ]
机构
[1] Univ Leicester, MRC Toxicol Unit, Leicester LE1 9HN, Leics, England
基金
英国医学研究理事会;
关键词
BCL2A1; BCL2; apoptosis; cancer; NF-KAPPA-B; CHRONIC LYMPHOCYTIC-LEUKEMIA; CHEMOTHERAPY-INDUCED APOPTOSIS; SQUAMOUS-CELL CARCINOMA; HUMAN MAST-CELLS; GENE-EXPRESSION; UP-REGULATION; PROTEIN A1; DIFFERENTIAL REGULATION; TRANSCRIPTIONAL TARGET;
D O I
10.1038/cdd.2011.158
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 kappa B (NF-kappa B) 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. Cell Death and Differentiation (2012) 19, 67-74; doi:10.1038/cdd.2011.158; published online 11 November 2011
引用
收藏
页码:67 / 74
页数:8
相关论文
共 103 条
[1]   The Bcl-2 apoptotic switch in cancer development and therapy [J].
Adams, J. M. ;
Cory, S. .
ONCOGENE, 2007, 26 (09) :1324-1337
[2]   The landscape of somatic copy-number alteration across human cancers [J].
Beroukhim, Rameen ;
Mermel, Craig H. ;
Porter, Dale ;
Wei, Guo ;
Raychaudhuri, Soumya ;
Donovan, Jerry ;
Barretina, Jordi ;
Boehm, Jesse S. ;
Dobson, Jennifer ;
Urashima, Mitsuyoshi ;
Mc Henry, Kevin T. ;
Pinchback, Reid M. ;
Ligon, Azra H. ;
Cho, Yoon-Jae ;
Haery, Leila ;
Greulich, Heidi ;
Reich, Michael ;
Winckler, Wendy ;
Lawrence, Michael S. ;
Weir, Barbara A. ;
Tanaka, Kumiko E. ;
Chiang, Derek Y. ;
Bass, Adam J. ;
Loo, Alice ;
Hoffman, Carter ;
Prensner, John ;
Liefeld, Ted ;
Gao, Qing ;
Yecies, Derek ;
Signoretti, Sabina ;
Maher, Elizabeth ;
Kaye, Frederic J. ;
Sasaki, Hidefumi ;
Tepper, Joel E. ;
Fletcher, Jonathan A. ;
Tabernero, Josep ;
Baselga, Jose ;
Tsao, Ming-Sound ;
Demichelis, Francesca ;
Rubin, Mark A. ;
Janne, Pasi A. ;
Daly, Mark J. ;
Nucera, Carmelo ;
Levine, Ross L. ;
Ebert, Benjamin L. ;
Gabriel, Stacey ;
Rustgi, Anil K. ;
Antonescu, Cristina R. ;
Ladanyi, Marc ;
Letai, Anthony .
NATURE, 2010, 463 (7283) :899-905
[3]   MYC-induced myeloid leukemogenesis is accelerated by all six members of the antiapoptotic BCL family [J].
Beverly, L. J. ;
Varmus, H. E. .
ONCOGENE, 2009, 28 (09) :1274-1279
[4]   Downregulation of Bfl-1 protein expression sensitizes malignant B cells to apoptosis [J].
Brien, G. ;
Trescol-Bierriont, M-C ;
Bonnefoy-Berard, N. .
ONCOGENE, 2007, 26 (39) :5828-5832
[5]   Characterization of Peptide Aptamers Targeting Bfl-1 Anti-Apoptotic Protein [J].
Brien, G. ;
Debaud, A. -L. ;
Bickle, M. ;
Trescol-Biemont, M-C ;
Moncorge, O. ;
Colas, P. ;
Bonnefoy-Berard, N. .
BIOCHEMISTRY, 2011, 50 (23) :5120-5129
[6]   C-terminal Residues Regulate Localization and Function of the Antiapoptotic Protein Bfl-1 [J].
Brien, Gaelle ;
Debaud, Anne-Laure ;
Robert, Xavier ;
Oliver, Lisa ;
Trescol-Biemont, Marie-Claude ;
Cauquil, Nicolas ;
Geneste, Olivier ;
Aghajari, Nushin ;
Vallette, Francois M. ;
Haser, Richard ;
Bonnefoy-Berard, Nathalie .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (44) :30257-30263
[7]   Prediction of metastatic relapse in node-positive breast cancer:: establishment of a clinicogenomic model after FEC100 adjuvant regimen [J].
Campone, Mario ;
Campion, Loic ;
Roche, Henry ;
Gouraud, Wilfried ;
Charbonnel, Catherine ;
Magrangeas, Florence ;
Minvielle, Stephane ;
Geneve, Jean ;
Martin, Anne-Laure ;
Bataille, Regis ;
Jezequel, Pascal .
BREAST CANCER RESEARCH AND TREATMENT, 2008, 109 (03) :491-501
[8]   Concurrent pregnancy retards mammary involution: Effects on apoptosis and proliferation of the mammary epithelium after forced weaning of mice [J].
Capuco, AV ;
Li, ML ;
Long, EH ;
Ren, SX ;
Hruska, KS ;
Schorr, K ;
Furth, PA .
BIOLOGY OF REPRODUCTION, 2002, 66 (05) :1471-1476
[9]   Inhibition of Bfl-1 with N-aryl maleimides [J].
Cashman, John R. ;
MacDonald, Mary ;
Ghirmai, Senait ;
Okolotowicz, Karl J. ;
Sergienko, Eduard ;
Brown, Brock ;
Garcia, Xochella ;
Zhai, Dayong ;
Dahl, Russell ;
Reed, John C. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (22) :6560-6564
[10]   Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members [J].
Certo, Michael ;
Moore, Victoria Del Gaizo ;
Nishino, Mari ;
Wei, Guo ;
Korsmeyer, Stanley ;
Armstrong, Scott A. ;
Letai, Anthony .
CANCER CELL, 2006, 9 (05) :351-365