The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The protein encoded by this gene binds to BCL2 and is referred to as BCL2-associated athanogene. It enhances the anti-apoptotic effects of BCL2 and represents a link between growth factor receptors and anti-apoptotic mechanisms. At least three protein isoforms are encoded by this mRNA through the use of alternative translation initiation sites, including a non-AUG site.[2]
Clinical significance
BAG gene has been implicated in age related neurodegenerative diseases as Alzheimer's. It has been demonstrated that BAG1 and BAG 3 regulate the proteasomal and lysosomal protein elimination pathways, respectively.[3]
↑Guzey M, Takayama S, Reed JC (Dec 2000). "BAG1L enhances trans-activation function of the vitamin D receptor". J. Biol. Chem. 275 (52): 40749–56. doi:10.1074/jbc.M004977200. PMID10967105.
↑Kullmann M, Schneikert J, Moll J, Heck S, Zeiner M, Gehring U, Cato AC (June 1998). "RAP46 is a negative regulator of glucocorticoid receptor action and hormone-induced apoptosis". J. Biol. Chem. 273 (23): 14620–5. doi:10.1074/jbc.273.23.14620. PMID9603979.
↑Takayama S, Xie Z, Reed JC (January 1999). "An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators". J. Biol. Chem. 274 (2): 781–6. doi:10.1074/jbc.274.2.781. PMID9873016.
↑Lin J, Hutchinson L, Gaston SM, Raab G, Freeman MR (August 2001). "BAG-1 is a novel cytoplasmic binding partner of the membrane form of heparin-binding EGF-like growth factor: a unique role for proHB-EGF in cell survival regulation". J. Biol. Chem. 276 (32): 30127–32. doi:10.1074/jbc.M010237200. PMID11340068.
↑Liu R, Takayama S, Zheng Y, Froesch B, Chen GQ, Zhang X, Reed JC, Zhang XK (July 1998). "Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic acid-induced apoptosis in cancer cells". J. Biol. Chem. 273 (27): 16985–92. doi:10.1074/jbc.273.27.16985. PMID9642262.
Clemo NK, Arhel NJ, Barnes JD, et al. (2005). "The role of the retinoblastoma protein (Rb) in the nuclear localization of BAG-1: implications for colorectal tumour cell survival". Biochem. Soc. Trans. 33 (Pt 4): 676–8. doi:10.1042/BST0330676. PMID16042572.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Takayama S, Kochel K, Irie S, et al. (1996). "Cloning of cDNAs encoding the human BAG1 protein and localization of the human BAG1 gene to chromosome 9p12". Genomics. 35 (3): 494–8. doi:10.1006/geno.1996.0389. PMID8812483.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Kullmann M, Schneikert J, Moll J, et al. (1998). "RAP46 is a negative regulator of glucocorticoid receptor action and hormone-induced apoptosis". J. Biol. Chem. 273 (23): 14620–5. doi:10.1074/jbc.273.23.14620. PMID9603979.
Liu R, Takayama S, Zheng Y, et al. (1998). "Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic acid-induced apoptosis in cancer cells". J. Biol. Chem. 273 (27): 16985–92. doi:10.1074/jbc.273.27.16985. PMID9642262.
Takayama S, Krajewski S, Krajewska M, et al. (1998). "Expression and location of Hsp70/Hsc-binding anti-apoptotic protein BAG-1 and its variants in normal tissues and tumor cell lines". Cancer Res. 58 (14): 3116–31. PMID9679980.
Takayama S, Xie Z, Reed JC (1999). "An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators". J. Biol. Chem. 274 (2): 781–6. doi:10.1074/jbc.274.2.781. PMID9873016.
Yang X, Pater A, Tang SC (1999). "Cloning and characterization of the human BAG-1 gene promoter: upregulation by tumor-derived p53 mutants". Oncogene. 18 (32): 4546–53. doi:10.1038/sj.onc.1202843. PMID10467399.
Lüders J, Demand J, Höhfeld J (2000). "The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome". J. Biol. Chem. 275 (7): 4613–7. doi:10.1074/jbc.275.7.4613. PMID10671488.