This gene encodes a member of the bcl2 protein family. The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators that are involved in a wide variety of cellular activities such as embryonic development, homeostasis and tumorigenesis. The protein encoded by this gene is able to reduce the release of pro-apoptotic cytochrome c from mitochondria and block caspase activation. This gene is a direct transcription target of NF-kappa B in response to inflammatory mediators, and has been shown to be up-regulated by different extracellular signals, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), CD40, phorbol ester and inflammatory cytokine TNF and IL-1, which suggests a cytoprotective function that is essential for lymphocyte activation as well as cell survival.[3]
In melanocytic cells BCL2A1 gene expression may be regulated by MITF.[4]
Interactions
BCL2-related protein A1 has been shown to interact with:
↑Savitsky K, Sfez S, Tagle DA, Ziv Y, Sartiel A, Collins FS, Shiloh Y, Rotman G (March 1996). "The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species". Hum Mol Genet. 4 (11): 2025–32. doi:10.1093/hmg/4.11.2025. PMID8589678.
↑Zhang H, Cowan-Jacob SW, Simonen M, Greenhalf W, Heim J, Meyhack B (2000). "Structural basis of BFL-1 for its interaction with BAX and its anti-apoptotic action in mammalian and yeast cells". J. Biol. Chem. 275 (15): 11092–9. doi:10.1074/jbc.275.15.11092. PMID10753914.
↑Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ (2001). "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis. 6 (5): 319–30. doi:10.1023/A:1011319901057. PMID11483855.
↑Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function". Mol. Cell. 17 (3): 393–403. doi:10.1016/j.molcel.2004.12.030. PMID15694340.
Choi SS, Park IC, Yun JW, et al. (1995). "A novel Bcl-2 related gene, Bfl-1, is overexpressed in stomach cancer and preferentially expressed in bone marrow". Oncogene. 11 (9): 1693–8. PMID7478596.
Lin EY, Orlofsky A, Berger MS, Prystowsky MB (1993). "Characterization of A1, a novel hemopoietic-specific early-response gene with sequence similarity to bcl-2". J. Immunol. 151 (4): 1979–88. PMID8345191.
Karsan A, Yee E, Kaushansky K, Harlan JM (1996). "Cloning of human Bcl-2 homologue: inflammatory cytokines induce human A1 in cultured endothelial cells". Blood. 87 (8): 3089–96. PMID8605321.
Karsan A, Yee E, Harlan JM (1996). "Endothelial cell death induced by tumor necrosis factor-alpha is inhibited by the Bcl-2 family member, A1". J. Biol. Chem. 271 (44): 27201–4. doi:10.1074/jbc.271.44.27201. PMID8910286.
Kenny JJ, Knobloch TJ, Augustus M, et al. (1997). "GRS, a novel member of the Bcl-2 gene family, is highly expressed in multiple cancer cell lines and in normal leukocytes". Oncogene. 14 (8): 997–1001. doi:10.1038/sj.onc.1200898. PMID9050999.
Choi SS, Park SH, Kim UJ, Shin HS (1997). "Bfl-1, a Bcl-2-related gene, is the human homolog of the murine A1, and maps to chromosome 15q24.3". Mamm. Genome. 8 (10): 781–2. doi:10.1007/s003359900567. PMID9321477.
Takemoto Y, Furuta M, Sato M, et al. (1998). "Growth factor receptor-bound protein 2 (Grb2) association with hemopoietic specific protein 1: linkage between Lck and Grb2". J. Immunol. 161 (2): 625–30. PMID9670936.
Holmgreen SP, Huang DC, Adams JM, Cory S (1999). "Survival activity of Bcl-2 homologs Bcl-w and A1 only partially correlates with their ability to bind pro-apoptotic family members". Cell Death Differ. 6 (6): 525–32. doi:10.1038/sj.cdd.4400519. PMID10381646.
Tomayko MM, Punt JA, Bolcavage JM, et al. (1999). "Expression of the Bcl-2 family member A1 is developmentally regulated in T cells". Int. Immunol. 11 (11): 1753–61. doi:10.1093/intimm/11.11.1753. PMID10545479.
Zhang H, Cowan-Jacob SW, Simonen M, et al. (2000). "Structural basis of BFL-1 for its interaction with BAX and its anti-apoptotic action in mammalian and yeast cells". J. Biol. Chem. 275 (15): 11092–9. doi:10.1074/jbc.275.15.11092. PMID10753914.
Duriez PJ, Wong F, Dorovini-Zis K, et al. (2000). "A1 functions at the mitochondria to delay endothelial apoptosis in response to tumor necrosis factor". J. Biol. Chem. 275 (24): 18099–107. doi:10.1074/jbc.M908925199. PMID10849436.
Harrington JJ, Sherf B, Rundlett S, et al. (2001). "Creation of genome-wide protein expression libraries using random activation of gene expression". Nat. Biotechnol. 19 (5): 440–5. doi:10.1038/88107. PMID11329013.
Bae J, Hsu SY, Leo CP, et al. (2001). "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis. 6 (5): 319–30. doi:10.1023/A:1011319901057. PMID11483855.
