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| | Immunohistochemical detection of human RCHY1 protein in non-small cell lung cancers. (A) squamous cell carcinoma, and (B) large cell carcinoma. |
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| Description | 261 amino acids; 32 kDa protein. |
| Expression | RCHY1 expresses at higher level in liver, testis and heart. Lower expression is detected in lung, brain, muscle and spleen. RCHY1 is overexpressed in non-small cell lung cancers. |
| Localisation | The localization of RCHY1 protein in human lung tumors was evaluated immunohistochemically. RCHY1 protein was found primarily in the cytoplasm and membrane and a small portion in the nucleus of malignant cells. |
| Function | RCHY1 is an ubiquitin-protein E3 ligase that promotes p53 degradation. The RCHY1 gene encodes a RING-H2 domain-containing protein with intrinsic ubiquitin-protein ligase activity. It has been reported that RCHY1( Pirh2) physically interacts with p53 and promotes ubiquitination of p53 independently of Mdm2. RCHY1 was also reported to be transactivated by the p53 product in MEFs, murine proB cell BaF3 and human BJT fibroblasts cells. Therefore, like MDM2, RCHY1 participates in an autoregulatory feedback loop that controls p53 function. Expression of RCHY1 decreased the level of p53 protein, while abrogation of endogenous RCHY1 expression increased the level of p53. Furthermore, RCHY1 represses p53 functions, including p53-dependent transactivation and growth inhibition. RCHY1 is overexpressed in both human and murine lung cancers by comparing Pirh2 mRNA and protein level between lung neoplastic tissues and uninvolved adjacent lung tissue. The increased RCHY1 protein could cause degradation of wild type p53 and reduce the tumor suppression function in tumor cells.
It has been reported that coexpression of RCHY1(ARNIP) and androgen receptor (AR) in COS-1 cells reduces the interaction between AR N- and C-terminus. The RING-H2 domain of the RCHY1 functions as an ubiquitin-protein ligase in vitro in the presence of a specific ubiquitin-conjugating enzyme, Ubc4-1. Mutation of a single cysteine residue in the RCHY RING-H2 domain (Cys145Ala) abolished this E3 ubiquitin ligase activity. Fluorescent protein tagging studies revealed that AR-RCHY1 interaction was hormone-independent in COS-1 cells, and suggest that co-localization of both AR and RCHY1to the nucleus upon androgen addition may allow RCHY1 to play a role in nuclear processes.
It has been reported that wild-type RCHY1is an unstable protein with a short half-life and coexpression of TIP60 enhances RCHY1 protein stability and alters RCHY1 subcellular localization. In addition, MVP (measles virus phosphoprotein ) is able to specifically interact with and stabilize the RCHY1 by preventing its ubiquitination. It has been reported that the RCHY1 also interacts with NTKL-BP1 (N-terminal kinase-like protein-binding protein 1) protein |
| Homology | It belongs to the ring finger ubiquitin protein E3 ligase family. Containing Conserved RING-finger Domain (residues 145 - 186 ) and CHY zinc finger (residues 20-94). |
| Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity. |
| Beitel LK, Elhaji YA, Lumbroso R, Wing SS, Panet-Raymond V, Gottlieb B, Pinsky L, Trifiro MA |
| Journal of molecular endocrinology. 2002 ; 29 (1) : 41-60. |
| PMID 12200228 |
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| Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. |
| Leng RP, Lin Y, Ma W, Wu H, Lemmers B, Chung S, Parant JM, Lozano G, Hakem R, Benchimol S |
| Cell. 2003 ; 112 (6) : 779-791. |
| PMID 12654245 |
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| Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer. |
| Duan W, Gao L, Druhan LJ, Zhu WG, Morrison C, Otterson GA, Villalona-Calero MA |
| Journal of the National Cancer Institute. 2004 ; 96 (22) : 1718-1721. |
| PMID 15547185 |
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| Control of human PIRH2 protein stability: involvement of TIP60 and the proteosome. |
| Logan IR, Sapountzi V, Gaughan L, Neal DE, Robson CN |
| The Journal of biological chemistry. 2004 ; 279 (12) : 11696-11704. |
| PMID 14701804 |
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| A new human gene hNTKL-BP1 interacts with hPirh2. |
| Zhang L, Li J, Wang C, Ma Y, Huo K |
| Biochemical and biophysical research communications. 2005 ; 330 (1) : 293-297. |
| PMID 15781263 |
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| Inhibition of ubiquitination and stabilization of human ubiquitin E3 ligase PIRH2 by measles virus phosphoprotein. |
| Chen M, Cortay JC, Logan IR, Sapountzi V, Robson CN, Gerlier D |
| Journal of virology. 2005 ; 79 (18) : 11824-11836. |
| PMID 16140759 |
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