BCL2-related protein A1 explained

Bcl-2-related protein A1 is a protein in humans which is encoded by the BCL2A1 gene.^{[1] [2] [3]}

Function

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 can 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 is 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:

• Bcl-2-associated X protein,^{[5] [6]} and
• Bcl-2-associated death promoter.^{[7] [8]}

Further reading

• Choi SS, Park IC, Yun JW . A novel Bcl-2 related gene, Bfl-1, is overexpressed in stomach cancer and preferentially expressed in bone marrow. . Oncogene . 11 . 9 . 1693–8 . 1995 . 7478596 . etal.
• Lin EY, Orlofsky A, Berger MS, Prystowsky MB . Characterization of A1, a novel hemopoietic-specific early-response gene with sequence similarity to bcl-2. . J. Immunol. . 151 . 4 . 1979–88 . 1993 . 10.4049/jimmunol.151.4.1979 . 8345191 . 22930599 .
• Karsan A, Yee E, Kaushansky K, Harlan JM . Cloning of human Bcl-2 homologue: inflammatory cytokines induce human A1 in cultured endothelial cells. . Blood . 87 . 8 . 3089–96 . 1996 . 10.1182/blood.V87.8.3089.bloodjournal8783089 . 8605321 . free .
• Karsan A, Yee E, Harlan JM . 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 . 1996 . 8910286 . 10.1074/jbc.271.44.27201 . free .
• Carrió R, López-Hoyos M, Jimeno J . A1 demonstrates restricted tissue distribution during embryonic development and functions to protect against cell death. . Am. J. Pathol. . 149 . 6 . 2133–42 . 1997 . 8952545 . 1865360 . etal.
• Kenny JJ, Knobloch TJ, Augustus M . 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 . 1997 . 9050999 . 10.1038/sj.onc.1200898 . 365249 . etal.
• Choi SS, Park SH, Kim UJ, Shin HS . 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 . 1997 . 9321477 . 10.1007/s003359900567 . 8472273 .
• Hsu SY, Kaipia A, McGee E . Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members. . Proc. Natl. Acad. Sci. U.S.A. . 94 . 23 . 12401–6 . 1997 . 9356461 . 24966 . 10.1073/pnas.94.23.12401 . 1997PNAS...9412401H . etal. free .
• Takemoto Y, Furuta M, Sato M . Growth factor receptor-bound protein 2 (Grb2) association with hemopoietic specific protein 1: linkage between Lck and Grb2. . J. Immunol. . 161 . 2 . 625–30 . 1998 . 10.4049/jimmunol.161.2.625 . 9670936 . 11576096 . etal.
• Zong WX, Edelstein LC, Chen C . The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-kappaB that blocks TNFalpha-induced apoptosis. . Genes Dev. . 13 . 4 . 382–7 . 1999 . 10049353 . 316475 . 10.1101/gad.13.4.382 . etal.
• Holmgreen SP, Huang DC, Adams JM, Cory S . 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 . 1999 . 10381646 . 10.1038/sj.cdd.4400519 . free .
• Lee HH, Dadgostar H, Cheng Q . NF-kappaB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes. . Proc. Natl. Acad. Sci. U.S.A. . 96 . 16 . 9136–41 . 1999 . 10430908 . 17745 . 10.1073/pnas.96.16.9136 . 1999PNAS...96.9136L . etal. free .
• Wang CY, Guttridge DC, Mayo MW, Baldwin AS . NF-kappaB induces expression of the Bcl-2 homologue A1/Bfl-1 to preferentially suppress chemotherapy-induced apoptosis. . Mol. Cell. Biol. . 19 . 9 . 5923–9 . 1999 . 10454539 . 84448 . 10.1128/MCB.19.9.5923.
• Tomayko MM, Punt JA, Bolcavage JM . Expression of the Bcl-2 family member A1 is developmentally regulated in T cells. . Int. Immunol. . 11 . 11 . 1753–61 . 1999 . 10545479 . 10.1093/intimm/11.11.1753 . etal. free .
• Zhang H, Cowan-Jacob SW, Simonen M . 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 . 2000 . 10753914 . 10.1074/jbc.275.15.11092 . etal. free .
• Duriez PJ, Wong F, Dorovini-Zis K . A1 functions at the mitochondria to delay endothelial apoptosis in response to tumor necrosis factor. . J. Biol. Chem. . 275 . 24 . 18099–107 . 2000 . 10849436 . 10.1074/jbc.M908925199 . etal. free .
• Harrington JJ, Sherf B, Rundlett S . Creation of genome-wide protein expression libraries using random activation of gene expression. . Nat. Biotechnol. . 19 . 5 . 440–5 . 2001 . 11329013 . 10.1038/88107 . 25064683 . etal.
• Bae J, Hsu SY, Leo CP . Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis. . Apoptosis . 6 . 5 . 319–30 . 2001 . 11483855 . 10.1023/A:1011319901057 . 23119757 . etal.
• Akari H, Bour S, Kao S . The human immunodeficiency virus type 1 accessory protein Vpu induces apoptosis by suppressing the nuclear factor kappaB-dependent expression of antiapoptotic factors. . J. Exp. Med. . 194 . 9 . 1299–311 . 2001 . 11696595 . 2195969 . 10.1084/jem.194.9.1299 . etal.

Notes and References

1. Savitsky K, Sfez S, Tagle DA, Ziv Y, Sartiel A, Collins FS, Shiloh Y, Rotman G . 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 . March 1996 . 8589678 . 10.1093/hmg/4.11.2025 .
2. Akatsuka Y, Nishida T, Kondo E, Miyazaki M, Taji H, Iida H, Tsujimura K, Yazaki M, Naoe T, Morishima Y, Kodera Y, Kuzushima K, Takahashi T . Identification of a polymorphic gene, BCL2A1, encoding two novel hematopoietic lineage-specific minor histocompatibility antigens . J Exp Med . 197 . 11 . 1489–500 . June 2003 . 12771180 . 2193899 . 10.1084/jem.20021925 .
3. Web site: Entrez Gene: BCL2A1 BCL2-related protein A1.
4. Hoek KS, Schlegel NC, Eichhoff OM . Novel MITF targets identified using a two-step DNA microarray strategy . Pigment Cell Melanoma Res. . 21 . 6 . 665–76 . 2008 . 19067971 . 10.1111/j.1755-148X.2008.00505.x . etal. free .
5. Aug 15, 1995 . Sedlak TW, Oltvai ZN, Yang E, Wang K, Boise LH, Thompson CB, Korsmeyer SJ . Multiple Bcl-2 family members demonstrate selective dimerizations with Bax . Proc. Natl. Acad. Sci. U.S.A. . 92 . 17 . 7834–8 . 7644501 . 41240 . 10.1073/pnas.92.17.7834. 1995PNAS...92.7834S . free .
6. Zhang H, Cowan-Jacob SW, Simonen M, Greenhalf W, Heim J, Meyhack B . 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 . 2000 . 10753914 . 10.1074/jbc.275.15.11092. free .
7. Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ . Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis . Apoptosis . 6 . 5 . 319–30 . 2001 . 11483855 . 10.1023/A:1011319901057. 23119757 .
8. Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC . Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function . Mol. Cell . 17 . 3 . 393–403 . 2005 . 15694340 . 10.1016/j.molcel.2004.12.030 . free .