The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress.
Recently, one study of the role of genetics in abdominal aortic aneurism (AAA) showed that different BAK1 variants can exist in both diseased and nondiseased AA tissues compared to matching blood samples. Since its publication, this observation has raised many discussions among scientific community because it seems to jeopardize the current paradigm that all cells have the same genomic DNA. However, BAK1 gene variants in different tissues may be easily explained by the expression of BAK1 gene on chromosome 6 and one its edited copies on chromosome 20. This conjecture reconciles both the current paradigm and the observation of BAK1 gene variation in different tissues. However, the authors of the BAK1 gene variations original article have published a response.
^Gottlieb B, Chalifour LE, Mitmaker B, Sheiner N, Obrand D, Abraham C, Meilleur M, Sugahara T, Bkaily G, Schweitzer M (July 2009). "BAK1 gene variation and abdominal aortic aneurysms". Hum. Mutat.30 (7): 1043–7. doi:10.1002/humu.21046. PMID19514060.
^ abHatchwell E (January 2010). "BAK1 gene variation and abdominal aortic aneurysms-variants are likely due to sequencing of a processed gene on chromosome 20". Hum. Mutat.31 (1): 108–9; author reply 110–1. doi:10.1002/humu.21147. PMID19847788.
^Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature437 (7062): 1173–8. doi:10.1038/nature04209. PMID16189514.
^Zheng TS (February 2001). "Death by design: the big debut of small molecules". Nat. Cell Biol.3 (2): E43–6. doi:10.1038/35055145.
^Lin B, Kolluri SK, Lin F, Liu W, Han YH, Cao X, Dawson MI, Reed JC, Zhang XK (February 2004). "Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3". Cell116 (4): 527–40. doi:10.1016/s0092-8674(04)00162-x. PMID14980220.
^Enyedy IJ, Ling Y, Nacro K, Tomita Y, Wu X, Cao Y, Guo R, Li B, Zhu X, Huang Y, Long YQ, Roller PP, Yang D, Wang S (December 2001). "Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening". J. Med. Chem.44 (25): 4313–24. doi:10.1021/jm010016f. PMID11728179.
^Weng C, Li Y, Xu D, Shi Y, Tang H (March 2005). "Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells". J. Biol. Chem.280 (11): 10491–500. doi:10.1074/jbc.M412819200. PMID15637055.
^Bae J, Leo CP, Hsu SY, Hsueh AJ (August 2000). "MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain". J. Biol. Chem.275 (33): 25255–61. doi:10.1074/jbc.M909826199. PMID10837489.
Buytaert E, Callewaert G, Vandenheede JR, Agostinis P (2007). "Deficiency in apoptotic effectors Bax and Bak reveals an autophagic cell death pathway initiated by photodamage to the endoplasmic reticulum". Autophagy2 (3): 238–40. PMID16874066.
Farrow SN, White JH, Martinou I et al. (1995). "Cloning of a bcl-2 homologue by interaction with adenovirus E1B 19K". Nature374 (6524): 731–3. doi:10.1038/374731a0. PMID7715729.
Diaz JL, Oltersdorf T, Horne W et al. (1997). "A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members". J. Biol. Chem.272 (17): 11350–5. doi:10.1074/jbc.272.17.11350. PMID9111042.
Shimizu S, Narita M, Tsujimoto Y (1999). "Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC". Nature399 (6735): 483–7. doi:10.1038/20959. PMID10365962.
Ohi N, Tokunaga A, Tsunoda H et al. (1999). "A novel adenovirus E1B19K-binding protein B5 inhibits apoptosis induced by Nip3 by forming a heterodimer through the C-terminal hydrophobic region". Cell Death Differ.6 (4): 314–25. doi:10.1038/sj.cdd.4400493. PMID10381623.
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.
Leo CP, Hsu SY, Chun SY et al. (1999). "Characterization of the antiapoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) and the stimulation of its message by gonadotropins in the rat ovary". Endocrinology140 (12): 5469–77. doi:10.1210/en.140.12.5469. PMID10579309.
Bae J, Leo CP, Hsu SY, Hsueh AJ (2000). "MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain". J. Biol. Chem.275 (33): 25255–61. doi:10.1074/jbc.M909826199. PMID10837489.
Degterev A, Lugovskoy A, Cardone M et al. (2001). "Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL". Nat. Cell Biol.3 (2): 173–82. doi:10.1038/35055085. PMID11175750.