Activator of apoptosis harakiri is a protein in humans that is encoded by HRK gene. 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.
The following HRK reagents supplied by CUSABIO are manufactured under a strict quality control system. Multiple applications have been validated and solid technical support is offered.
HRK Antibodies for Homo sapiens (Human)
Code | Product Name | Species Reactivity | Application |
---|---|---|---|
CSB-PA297560 | HRK Antibody |
Human | ELISA,IHC |
CSB-PA561475 | HRK Antibody |
Human | ELISA,IHC |
HRK Proteins for Homo sapiens (Human)
Code | Product Name | Source |
---|---|---|
CSB-CF010741HU | Recombinant Human Activator of apoptosis harakiri (HRK) |
in vitro E.coli expression system |
CSB-YP010741HU1 CSB-EP010741HU1 CSB-BP010741HU1 CSB-MP010741HU1 CSB-EP010741HU1-B |
Recombinant Human Activator of apoptosis harakiri (HRK), partial |
Yeast E.coli Baculovirus Mammalian cell In Vivo Biotinylation in E.coli |
HRK Proteins for Mus musculus (Mouse)
Code | Product Name | Source |
---|---|---|
CSB-CF010741MO | Recombinant Mouse Activator of apoptosis harakiri (Hrk) |
in vitro E.coli expression system |
CSB-YP010741MO1 CSB-EP010741MO1 CSB-BP010741MO1 CSB-MP010741MO1 CSB-EP010741MO1-B |
Recombinant Mouse Activator of apoptosis harakiri (Hrk), partial |
Yeast E.coli Baculovirus Mammalian cell In Vivo Biotinylation in E.coli |
HRK Proteins for Rattus norvegicus (Rat)
Code | Product Name | Source |
---|---|---|
CSB-CF010741RA | Recombinant Rat Activator of apoptosis harakiri (Hrk) |
in vitro E.coli expression system |
CSB-YP010741RA1 CSB-EP010741RA1 CSB-BP010741RA1 CSB-MP010741RA1 CSB-EP010741RA1-B |
Recombinant Rat Activator of apoptosis harakiri (Hrk), partial |
Yeast E.coli Baculovirus Mammalian cell In Vivo Biotinylation in E.coli |
Harakiri (HRK) is a BH3-only protein of the Bcl-2 family. HRK localizes to membranes of intracellular organelles in a pattern similar to that previously reported for BCL2 and BCLXL. HRK mRNA was expressed in the pancreas and at very low or undetectable levels in the kidney, liver, lung, and brain [1]. This showed that HRK displays a highly restricted expression in human tissues [1]. Lack of conserved BH1 and BH2 regions, the HRK protein exhibits little 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 [1]. As an activator of apoptosis, HRK regulates apoptosis through interaction with death-repressor proteins Bcl-2 and Bcl-X(L) via the BH3 domain, but not with the death-promoting BCL2-related proteins BAX, BAK, or BCLXS [2-4]. Deletion of 16 amino acids, including the conserved BH3 region, abolished the ability of HRK to interact with Bcl‐2 and Bcl‐XL in mammalian cells [1]. Moreover, the killing activity of this mutant form of HRK was eliminated or dramatically reduced, suggesting that HRK activates cell death at least in part by interacting with and inhibiting the protection afforded by Bcl‐2 and Bcl‐XL [1]. It has been documented that HRK expression is suppressed by loss of heterozygosity and promoter hypermethylation in some cancers, including GBM [5-7]. Ezgi Kaya-Aksoy et al. demonstrated that HRK is differentially expressed in different GBM cell subpopulations and cooperates with TRAIL to induce cell death in GBM cells [8]. And their results also suggest that HRK overexpression decreases GBM tumors growth in vivo [8].
[1] Naohiro Inohara, Liyun Ding, et al. Harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival‐promoting proteins Bcl‐2 and Bcl‐XL [J]. EMBO J 1997, 16:1686-1694.
[2] 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‐XL [J]. EMBO J. 1997, 16, 1686-1694.
[3] Vo, T. T. & Letai, A. BH3-only proteins and their effects on cancer [J]. Adv. Exp. Med. Biol. 2010, 687, 49-63.
[4] Certo, M. et al. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members [J]. Cancer Cell 2006, 9, 351-365.
[5] Xu, M. et al. Synergistic silencing by promoter methylation and reduced AP-2α transactivation of the proapoptotic HRK gene confers apoptosis resistance and enhanced tumor growth [J]. Am. J. Pathol. 2013, 182, 84-95.
[6] Nakamura, M. et al. Defective expression of HRK is associated with promoter methylation in primary central nervous system lymphomas [J]. Oncology 2006, 70, 212-221.
[7] Hervouet, E., Vallette, , et al. Impact of the DNA methyltransferases expression on the methylation status of apoptosis-associated genes in glioblastoma multiforme [J]. Cell Death Dis. 2010, 1, e8-e8.
[8] Ezgi Kaya-Aksoy, Ahmet Cingoz, et al. The pro-apoptotic Bcl-2 family member Harakiri (HRK) induces cell death in glioblastoma multiforme [J]. Cell Death Discovery 2019, 5, 64.