Activator of apoptosis Hrk regulates apoptosis through interaction with death-repressor proteins Bcl-2 and Bcl-X(L). The HRK protein lacks significant homology to other BCL2 family members except for an 8-amino acid region that was similar to the BCL2 homology domain-3 (BH3) motif of BIK. HRK interacts with BCL2 and BCLXL via the BH3 domain, but not with the death-promoting BCL2-related proteins BAX, BAK, or BCLXS. HRK localizes to membranes of intracellular organelles in a pattern similar to that previously reported for BCL2 and BCLXL.[2]
↑Whitfield J, Harada K, Bardelle C, Staddon JM (Nov 2003). "High-throughput methods to detect dimerization of Bcl-2 family proteins". Anal. Biochem. 322 (2): 170–8. doi:10.1016/j.ab.2003.07.014. PMID14596824.
↑Imaizumi K, Morihara T, Mori Y, Katayama T, Tsuda M, Furuyama T, Wanaka A, Takeda M, Tohyama M (Mar 1999). "The cell death-promoting gene DP5, which interacts with the BCL2 family, is induced during neuronal apoptosis following exposure to amyloid beta protein". J. Biol. Chem. 274 (12): 7975–81. doi:10.1074/jbc.274.12.7975. PMID10075695.
↑Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (Feb 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.
Further reading
Imaizumi K, Morihara T, Mori Y, Katayama T, Tsuda M, Furuyama T, Wanaka A, Takeda M, Tohyama M (1999). "The cell death-promoting gene DP5, which interacts with the BCL2 family, is induced during neuronal apoptosis following exposure to amyloid beta protein". J. Biol. Chem. 274 (12): 7975–81. doi:10.1074/jbc.274.12.7975. PMID10075695.
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.
Wakabayashi T, Kosaka J, Hommura S (2002). "Up-regulation of Hrk, a regulator of cell death, in retinal ganglion cells of axotomized rat retina". Neurosci. Lett. 318 (2): 77–80. doi:10.1016/S0304-3940(01)02487-9. PMID11796190.
Sanz C, Horita M, Fernandez-Luna JL (2004). "Fas signaling and blockade of Bcr-Abl kinase induce apoptotic Hrk protein via DREAM inhibition in human leukemia cells". Haematologica. 87 (9): 903–7. PMID12217801.
Jurisicova A, Antenos M, Varmuza S, Tilly JL, Casper RF (2003). "Expression of apoptosis-related genes during human preimplantation embryo development: potential roles for the Harakiri gene product and Caspase-3 in blastomere fragmentation". Mol. Hum. Reprod. 9 (3): 133–41. doi:10.1093/molehr/gag016. PMID12606589.
Whitfield J, Harada K, Bardelle C, Staddon JM (2004). "High-throughput methods to detect dimerization of Bcl-2 family proteins". Anal. Biochem. 322 (2): 170–8. doi:10.1016/j.ab.2003.07.014. PMID14596824.
Obata T, Toyota M, Satoh A, Sasaki Y, Ogi K, Akino K, Suzuki H, Murai M, Kikuchi T, Mita H, Itoh F, Issa JP, Tokino T, Imai K (2004). "Identification of HRK as a target of epigenetic inactivation in colorectal and gastric cancer". Clin. Cancer Res. 9 (17): 6410–8. PMID14695142.
Sunayama J, Ando Y, Itoh N, Tomiyama A, Sakurada K, Sugiyama A, Kang D, Tashiro F, Gotoh Y, Kuchino Y, Kitanaka C (2005). "Physical and functional interaction between BH3-only protein Hrk and mitochondrial pore-forming protein p32". Cell Death Differ. 11 (7): 771–81. doi:10.1038/sj.cdd.4401418. PMID15031724.
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.
Kuwana T, Bouchier-Hayes L, Chipuk JE, Bonzon C, Sullivan BA, Green DR, Newmeyer DD (2005). "BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly". Mol. Cell. 17 (4): 525–35. doi:10.1016/j.molcel.2005.02.003. PMID15721256.
Certo M, Del Gaizo Moore V, Nishino M, Wei G, Korsmeyer S, Armstrong SA, Letai A (2006). "Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members". Cancer Cell. 9 (5): 351–65. doi:10.1016/j.ccr.2006.03.027. PMID16697956.