HRK (gene) explained

Activator of apoptosis harakiri is a protein that in humans is encoded by the HRK gene.^{[1] [2]}

Function

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]

Interactions

HRK (gene) has been shown to interact with:

• BCL2-like 1,^{[3] [4]} and
• Bcl-2.^{[1] [5]}

Further reading

• Imaizumi K, Morihara T, Mori Y, Katayama T, Tsuda M, Furuyama T, Wanaka A, Takeda M, Tohyama M . 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 . 1999 . 10075695 . 10.1074/jbc.274.12.7975 . free .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination. . Genome Res. . 10 . 11 . 1788–95 . 2001 . 11076863 . 310948 . 10.1101/gr.143000 .
• Sanz C, Mellstrom B, Link WA, Naranjo JR, Fernandez-Luna JL . Interleukin 3-dependent activation of DREAM is involved in transcriptional silencing of the apoptotic Hrk gene in hematopoietic progenitor cells. . EMBO J. . 20 . 9 . 2286–92 . 2001 . 11331593 . 125442 . 10.1093/emboj/20.9.2286 .
• 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 .
• Wakabayashi T, Kosaka J, Hommura S . Up-regulation of Hrk, a regulator of cell death, in retinal ganglion cells of axotomized rat retina. . Neurosci. Lett. . 318 . 2 . 77–80 . 2002 . 11796190 . 10.1016/S0304-3940(01)02487-9 . 45375137 .
• Sanz C, Horita M, Fernandez-Luna JL . Fas signaling and blockade of Bcr-Abl kinase induce apoptotic Hrk protein via DREAM inhibition in human leukemia cells. . Haematologica . 87 . 9 . 903–7 . 2004 . 12217801 .
• Jurisicova A, Antenos M, Varmuza S, Tilly JL, Casper RF . 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 . 2003 . 12606589 . 10.1093/molehr/gag016 . free .
• Whitfield J, Harada K, Bardelle C, Staddon JM . High-throughput methods to detect dimerization of Bcl-2 family proteins. . Anal. Biochem. . 322 . 2 . 170–8 . 2004 . 14596824 . 10.1016/j.ab.2003.07.014 .
• 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 . Identification of HRK as a target of epigenetic inactivation in colorectal and gastric cancer. . Clin. Cancer Res. . 9 . 17 . 6410–8 . 2004 . 14695142 .
• Sunayama J, Ando Y, Itoh N, Tomiyama A, Sakurada K, Sugiyama A, Kang D, Tashiro F, Gotoh Y, Kuchino Y, Kitanaka C . Physical and functional interaction between BH3-only protein Hrk and mitochondrial pore-forming protein p32. . Cell Death Differ. . 11 . 7 . 771–81 . 2005 . 15031724 . 10.1038/sj.cdd.4401418 . free .
• 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 .
• Kuwana T, Bouchier-Hayes L, Chipuk JE, Bonzon C, Sullivan BA, Green DR, Newmeyer DD . BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. . Mol. Cell . 17 . 4 . 525–35 . 2005 . 15721256 . 10.1016/j.molcel.2005.02.003 . free .
• Certo M, Del Gaizo Moore V, Nishino M, Wei G, Korsmeyer S, Armstrong SA, Letai A . Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. . Cancer Cell . 9 . 5 . 351–65 . 2006 . 16697956 . 10.1016/j.ccr.2006.03.027 . free .

Notes and References

1. Inohara N, Ding L, Chen S, Núñez G . harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L) . EMBO J . 16 . 7 . 1686–94 . May 1997 . 9130713 . 1169772 . 10.1093/emboj/16.7.1686 .
2. Web site: Entrez Gene: HRK harakiri, BCL2 interacting protein (contains only BH3 domain).
3. Whitfield J, Harada K, Bardelle C, Staddon JM . High-throughput methods to detect dimerization of Bcl-2 family proteins . Anal. Biochem. . 322 . 2 . 170–8 . Nov 2003 . 14596824 . 10.1016/j.ab.2003.07.014.
4. Imaizumi K, Morihara T, Mori Y, Katayama T, Tsuda M, Furuyama T, Wanaka A, Takeda M, Tohyama M . 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 . Mar 1999 . 10075695 . 10.1074/jbc.274.12.7975. free .
5. 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 . Feb 2005 . 15694340 . 10.1016/j.molcel.2004.12.030 . free .