Genomes and Genes
Gene Symbol: SIAH1
Description: siah E3 ubiquitin protein ligase 1
Alias: SIAH1A, E3 ubiquitin-protein ligase SIAH1, RING-type E3 ubiquitin transferase SIAH1, seven in absentia homolog 1, siah-1a
- Germani A, Prabel A, Mourah S, Podgorniak M, Di Carlo A, Ehrlich R, et al. SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway. Oncogene. 2003;22:8845-51 pubmed..Our results suggest that p21(Waf-1/Cip-1) induction by SIAH-1 could not be mediated by CtIP degradation. ..
- Kim C, Cho Y, Park C, Jeong S, Nam S, Kim S, et al. Inactivating mutations of the Siah-1 gene in gastric cancer. Oncogene. 2004;23:8591-6 pubmed..These data suggest that inactivating mutations of the Siah-1 may contribute to the development of gastric cancer through beta-catenin stabilization and apoptosis block. ..
- Hara M, Agrawal N, Kim S, Cascio M, Fujimuro M, Ozeki Y, et al. S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat Cell Biol. 2005;7:665-74 pubmed..NO) generation that follows apoptotic stimulation elicits S-nitrosylation of GAPDH, which triggers binding to Siah1 (an E3 ubiquitin ligase), nuclear translocation and apoptosis...
- Matsuzawa S, Li C, Ni C, Takayama S, Reed J, Ely K. Structural analysis of Siah1 and its interactions with Siah-interacting protein (SIP). J Biol Chem. 2003;278:1837-40 pubmed..In Siah1 a large concave surface is formed across the dimer interface...
- House C, Hancock N, Möller A, Cromer B, Fedorov V, Bowtell D, et al. Elucidation of the substrate binding site of Siah ubiquitin ligase. Structure. 2006;14:695-701 pubmed..Mutagenesis of Siah at sites of interaction also abrogates both in vitro peptide binding and destabilization of a known Siah target. ..
- Boehm J, He Y, Greiner A, Staudt L, Wirth T. Regulation of BOB.1/OBF.1 stability by SIAH. EMBO J. 2001;20:4153-62 pubmed..In support of this suggestion we have been able to identify two related BOB.1/OBF.1 interacting proteins, SIAH1 and SIAH2, in a yeast two-hybrid screen. SIAH1 and SIAH2 are known regulators of protein stability...
- Winter M, Sombroek D, Dauth I, Moehlenbrink J, Scheuermann K, Crone J, et al. Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR. Nat Cell Biol. 2008;10:812-24 pubmed publisher..Our results provide a molecular framework for HIPK2 regulation in unstressed and damaged cells. ..
- Calzado M, de La Vega L, Möller A, Bowtell D, Schmitz M. An inducible autoregulatory loop between HIPK2 and Siah2 at the apex of the hypoxic response. Nat Cell Biol. 2009;11:85-91 pubmed publisher..As HIPK2 has an important role as a negative regulator of gene expression, its elimination from promoter-associated repressor complexes allows the induction of a substantial fraction of hypoxia-induced genes. ..
- Wen Y, Yang Z, Song M, Li B, Zhu J, Wang E. SIAH1 induced apoptosis by activation of the JNK pathway and inhibited invasion by inactivation of the ERK pathway in breast cancer cells. Cancer Sci. 2010;101:73-9 pubmed publisherb>Seven in absentia homolog 1 (SIAH1), a homologue of Drosophila seven in absentia (Sina), has emerged as a tumor suppressor and plays an important role in regulating cell apoptosis...
- Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S, et al. hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways. Mol Cell Biol. 1999;19:3798-807 pubmed..Although the Vav-interacting domain is located in the C-terminal portion of hSiah2, the N-terminal region of hSiah2 is necessary for the inhibitory role that seems to be independent of the proteasome degradation. ..
- Lee J, Wheeler T, Li L, Chin L. Ubiquitination of alpha-synuclein by Siah-1 promotes alpha-synuclein aggregation and apoptotic cell death. Hum Mol Genet. 2008;17:906-17 pubmed..Our findings suggest that Siah-1-mediated alpha-synuclein ubiquitination may play a critical role in Lewy body formation and PD pathogenesis. ..
- Liu M, Hsu J, Chan C, Li Z, Zhou Q. The ubiquitin ligase Siah1 controls ELL2 stability and formation of super elongation complexes to modulate gene transcription. Mol Cell. 2012;46:325-34 pubmed publisher..Here we identify the RING domain protein Siah1, but not the homologous Siah2, as the E3 ubiquitin ligase for ELL2 polyubiquitination and proteasomal degradation...
- Wang D, Wang Y, Kong T, Fan F, Jiang Y. Hypoxia-induced ?-catenin downregulation involves p53-dependent activation of Siah-1. Cancer Sci. 2011;102:1322-8 pubmed publisher..Together, the results suggest that hypoxia downregulates ?-catenin by increasing Siah-1 expression in a p53-dependent manner. ..
- Moller A, House C, Wong C, Scanlon D, Liu M, Ronai Z, et al. Inhibition of Siah ubiquitin ligase function. Oncogene. 2009;28:289-96 pubmed publisher..These data show, in a proof-of-principle study, that Siah protein, the most upstream component of the hypoxia pathway yet identified, is a viable drug target for antitumor therapies. ..
- Hu G, Zhang S, Vidal M, Baer J, Xu T, Fearon E. Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway. Genes Dev. 1997;11:2701-14 pubmed..Taken together, the data imply that the Sina/Siah proteins regulate DCC and perhaps other proteins via the ubiquitin-proteasome pathway. ..
- Wen Y, Yang Z, Song M, Li B, Yao X, Chen X, et al. The expression of SIAH1 is downregulated and associated with Bim and apoptosis in human breast cancer tissues and cells. Mol Carcinog. 2010;49:440-9 pubmed publisherSeven in absentia homolog1 (SIAH1) was reported as a tumor suppressor and played an important role in regulating cell apoptosis. However, its effects on the breast carcinogenesis remain unclear...
- Nemani M, Linares Cruz G, Bruzzoni Giovanelli H, Roperch J, Tuynder M, Bougueleret L, et al. Activation of the human homologue of the Drosophila sina gene in apoptosis and tumor suppression. Proc Natl Acad Sci U S A. 1996;93:9039-42 pubmed..A similar pattern of expression is also displayed by the p21waf1. These results suggest that mammalian seven in absentia gene, which is a target for activation by p53, may play a role in apoptosis and tumor suppression. ..
- Medhioub M, Vaury C, Hamelin R, Thomas G. Lack of somatic mutation in the coding sequence of SIAH1 in tumors hemizygous for this candidate tumor suppressor gene. Int J Cancer. 2000;87:794-7 pubmedThe human homolog of the Drosophila seven in absentia gene (SIAH1) may play an important role in apoptosis and tumor suppression...
- Nagano Y, Yamashita H, Takahashi T, Kishida S, Nakamura T, Iseki E, et al. Siah-1 facilitates ubiquitination and degradation of synphilin-1. J Biol Chem. 2003;278:51504-14 pubmed..Siah-1 was found to abrogate the inhibitory effects of synphilin-1 on dopamine release. Such findings suggest that Siah-1 might play a role in regulation of synphilin-1 function. ..
- Xu Z, Sproul A, Wang W, Kukekov N, Greene L. Siah1 interacts with the scaffold protein POSH to promote JNK activation and apoptosis. J Biol Chem. 2006;281:303-12 pubmed..Here, we show that Siah1 is a binding partner for POSH (plenty of SH3s), a scaffold component of the apoptotic JNK pathway, and that Siah ..
- Famulski J, Trivedi N, Howell D, Yang Y, Tong Y, Gilbertson R, et al. Siah regulation of Pard3A controls neuronal cell adhesion during germinal zone exit. Science. 2010;330:1834-8 pubmed publisher..Our findings define a Siah-Pard3A signaling pathway that controls adhesion-dependent exit of neuronal progenitors or immature neurons from a germinal zone niche. ..
- Germani A, Bruzzoni Giovanelli H, Fellous A, Gisselbrecht S, Varin Blank N, Calvo F. SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis. Oncogene. 2000;19:5997-6006 pubmed..Our results imply, for the first time, SIAH-1 in regulating the degradation of proteins directly implicated in the mitotic process. ..
- Wheeler T, Chin L, Li Y, Roudabush F, Li L. Regulation of synaptophysin degradation by mammalian homologues of seven in absentia. J Biol Chem. 2002;277:10273-82 pubmed..Our findings indicate that Siah proteins function as E3 ubiquitin-protein ligases to regulate the ubiquitination and degradation of synaptophysin. ..
- Dimitrova Y, Li J, Lee Y, Rios Esteves J, Friedman D, Choi H, et al. Direct ubiquitination of beta-catenin by Siah-1 and regulation by the exchange factor TBL1. J Biol Chem. 2010;285:13507-16 pubmed publisher..Siah-1 and TBL1 were found to bind to the same armadillo repeat domain of beta-catenin, suggesting that polyubiquitination of beta-catenin is regulated by competition between Siah-1 and TBL1 during Wnt signaling. ..
- Brauckhoff A, Ehemann V, Schirmacher P, Breuhahn K. [Reduced expression of the E3-ubiquitin ligase seven in absentia homologue (SIAH)-1 in human hepatocellular carcinoma]. Verh Dtsch Ges Pathol. 2007;91:269-77 pubmed..Therefore we conclude that distinct SIAH-1 levels mediate pro-tumorigenic effects in HCC cells and that further SIAH-1 inhibition may represent a new therapeutic strategy in the treatment of human hepatocellular carcinoma. ..
- Matsuzawa S, Reed J. Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses. Mol Cell. 2001;7:915-26 pubmed..Expression of Siah is induced by p53, revealing a way of linking genotoxic injury to destruction of beta-catenin, thus reducing activity of Tcf/LEF transcription factors and contributing to cell cycle arrest. ..
- Fiucci G, Beaucourt S, Duflaut D, Lespagnol A, Stumptner Cuvelette P, Géant A, et al. Siah-1b is a direct transcriptional target of p53: identification of the functional p53 responsive element in the siah-1b promoter. Proc Natl Acad Sci U S A. 2004;101:3510-5 pubmed..Thus, the siah-1b gene is a direct transcriptional target of p53. ..
- Szargel R, Rott R, Eyal A, Haskin J, Shani V, Balan L, et al. Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates alpha-synuclein monoubiquitylation and inclusion formation. J Biol Chem. 2009;284:11706-16 pubmed publisher..Our results suggest a novel function for synphilin-1A as a regulator of SIAH activity and formation of Lewy body-like inclusions. ..
- Matsuo K, Satoh S, Okabe H, Nomura A, Maeda T, Yamaoka Y, et al. SIAH1 inactivation correlates with tumor progression in hepatocellular carcinomas. Genes Chromosomes Cancer. 2003;36:283-91 pubmed..1 as TSG candidates. Among these, the expression of SIAH1 was markedly downregulated in HCCs, and inactivation of SIAH1 expression was associated with LOH at 16q12.1...
- Hu G, Chung Y, Glover T, Valentine V, Look A, Fearon E. Characterization of human homologs of the Drosophila seven in absentia (sina) gene. Genomics. 1997;46:103-11 pubmed..We have characterized two highly conserved human homologs of sina, termed SIAH1 and SIAH2...
- Hu G, Fearon E. Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins. Mol Cell Biol. 1999;19:724-32 pubmed..The data indicate that the Siah-1 N-terminal RING domain is required for its proteolysis function, while the C-terminal sequences regulate oligomerization and binding to target proteins, such as DCC. ..
- Tuynder M, Susini L, Prieur S, Besse S, Fiucci G, Amson R, et al. Biological models and genes of tumor reversion: cellular reprogramming through tpt1/TCTP and SIAH-1. Proc Natl Acad Sci U S A. 2002;99:14976-81 pubmed
- Schmidt R, Park C, Ahmed A, Gundelach J, Reed N, Cheng S, et al. Inhibition of RAS-mediated transformation and tumorigenesis by targeting the downstream E3 ubiquitin ligase seven in absentia homologue. Cancer Res. 2007;67:11798-810 pubmed..Thus, SIAH may offer a novel therapeutic target to halt tumor growth and ameliorate RAS-mediated pancreatic cancer. ..
- Yun S, Möller A, Chae S, Hong W, Bae Y, Bowtell D, et al. Siah proteins induce the epidermal growth factor-dependent degradation of phospholipase Cepsilon. J Biol Chem. 2008;283:1034-42 pubmed..The EGF-dependent degradation of PLCepsilon was blocked in mouse embryonic fibroblast (MEF) cells derived from Siah1a/Siah2 double knockout mice, and the extrinsic expression of wild-type Siah1 restored the degradation of PLCepsilon,..
- Liu J, Stevens J, Rote C, Yost H, Hu Y, Neufeld K, et al. Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein. Mol Cell. 2001;7:927-36 pubmed..These results indicate that APC and Siah-1 mediate a novel beta-catenin degradation pathway linking p53 activation to cell cycle control. ..
- Buchwald M, Pietschmann K, Brand P, Gunther A, Mahajan N, Heinzel T, et al. SIAH ubiquitin ligases target the nonreceptor tyrosine kinase ACK1 for ubiquitinylation and proteasomal degradation. Oncogene. 2013;32:4913-20 pubmed publisher..Here we report that ACK1 and SIAH1 from Homo sapiens interact in a yeast two-hybrid screen...
- Fanelli M, Fantozzi A, De Luca P, Caprodossi S, Matsuzawa S, Lazar M, et al. The coiled-coil domain is the structural determinant for mammalian homologues of Drosophila Sina-mediated degradation of promyelocytic leukemia protein and other tripartite motif proteins by the proteasome. J Biol Chem. 2004;279:5374-9 pubmed..These results identify PML and other TRIMs as new factors post-translationally regulated by SIAH and involve the coiled-coil region of PML and of other SIAH substrates as a novel structural determinant for targeted degradation. ..
- Pepper I, Van Sciver R, Tang A. Phylogenetic analysis of the SINA/SIAH ubiquitin E3 ligase family in Metazoa. BMC Evol Biol. 2017;17:182 pubmed publisher..Vertebrate SIAH1, 2, and 3 are the three orthologs to invertebrate SINA protein...
- Szargel R, Shani V, Abd Elghani F, Mekies L, Liani E, Rott R, et al. The PINK1, synphilin-1 and SIAH-1 complex constitutes a novel mitophagy pathway. Hum Mol Genet. 2016;25:3476-3490 pubmed publisher..Drugs that activate this pathway will provide a novel strategy to promote the clearance of damaged mitochondria in Parkinson's disease. ..
- Adam M, Matt S, Christian S, Hess Stumpp H, Haegebarth A, Hofmann T, et al. SIAH ubiquitin ligases regulate breast cancer cell migration and invasion independent of the oxygen status. Cell Cycle. 2015;14:3734-47 pubmed publisher..In addition, SIAH inhibition reduced metastasis in melanoma. The role of SIAH1 in breast cancer is still ambiguous; both tumorigenic and tumor suppressive functions have been reported...
- Bae B, Hara M, Cascio M, Wellington C, Hayden M, Ross C, et al. Mutant huntingtin: nuclear translocation and cytotoxicity mediated by GAPDH. Proc Natl Acad Sci U S A. 2006;103:3405-9 pubmed..the nuclear translocation and associated cytotoxicity of mHtt reflect a ternary complex of mHtt with GAPDH and Siah1, a ubiquitin-E3-ligase...
- Wu H, Shi Y, Lin Y, Qian W, Yu Y, Huo K. Eukaryotic translation elongation factor 1 delta inhibits the ubiquitin ligase activity of SIAH-1. Mol Cell Biochem. 2011;357:209-15 pubmed publisher..Furthermore, EEF1D was able to inhibit the degradation of HPH2, a known substrate of SIAH-1. Taken together, our data suggest EFF1D functions as a novel negative regulator of SIAH-1. ..
- Knauer S, Mahendrarajah N, Roos W, KrÃ¤mer O. The inducible E3 ubiquitin ligases SIAH1 and SIAH2 perform critical roles in breast and prostate cancers. Cytokine Growth Factor Rev. 2015;26:405-13 pubmed publisher..An increasing body of evidence suggests that the E3 ubiquitin ligases SIAH1 and SIAH2 are able to dictate the growth, development, and chemo-/radiosensitivity of breast and prostate cancer ..
- He H, Fokas E, You A, Engenhart Cabillic R, An H. Siah1 proteins enhance radiosensitivity of human breast cancer cells. BMC Cancer. 2010;10:403 pubmed publisherSiah proteins play an important role in cancer progression. We evaluated the effect of Siah1, its splice variants Siah1L and the Siah1 mutant with the RING finger deleted (Siah1DeltaR) on radiosensitization of human breast cancer cells...
- Zhao J, Wang C, Wang J, Yang X, Diao N, Li Q, et al. E3 ubiquitin ligase Siah-1 facilitates poly-ubiquitylation and proteasomal degradation of the hepatitis B viral X protein. FEBS Lett. 2011;585:2943-50 pubmed publisher..Moreover, Siah-1 participated in p53-mediated HBx degradation. Therefore, Siah-1 may play important roles in ubiquitin-dependent degradation of HBx and may be involved in suppressing the progression of hepatocellular carcinoma (HCC)...
- Sun Q, Bai J, Lv R. Hedgehog/Gli1 signal pathway facilitates proliferation, invasion, and migration of cutaneous SCC through regulating VEGF. Tumour Biol. 2016;: pubmed..05). Abnormal activation of the HH signaling pathway plays critical roles in development of cutaneous SCC either in vivo or in vitro. ..
- Ohashi J, Naka I, Tsuchiya N. The impact of natural selection on an ABCC11 SNP determining earwax type. Mol Biol Evol. 2011;28:849-57 pubmed publisher..A recent genome-wide scan for positive selection revealed that a genomic region spanning ABCC11, LONP2, and SIAH1 genes has been subjected to a selective sweep in East Asians...
- Ko S, Isozaki K, Kim I, Lee J, Cho H, Sohn S, et al. PKC phosphorylation regulates mGluR5 trafficking by enhancing binding of Siah-1A. J Neurosci. 2012;32:16391-401 pubmed publisher..Thus CaM-regulated Siah-1A binding to mGluR5 dynamically regulates mGluR5 trafficking. These findings support a conserved role for CaM in regulating mGluR trafficking by PKC-dependent regulation of receptor-binding proteins. ..
- Kramer O, Müller S, Buchwald M, Reichardt S, Heinzel T. Mechanism for ubiquitylation of the leukemia fusion proteins AML1-ETO and PML-RARalpha. FASEB J. 2008;22:1369-79 pubmed..Our observations shed light on the mechanism determining the interplay between E2-conjugases, E3-ligases, and their substrates and suggest a strategy for utilizing the ubiquitylation machinery in a therapeutic setting. ..
- Jarmuz A, Chester A, Bayliss J, Gisbourne J, Dunham I, Scott J, et al. An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22. Genomics. 2002;79:285-96 pubmed..Tissue-specific expression of these genes in a variety of cell lines, along with other evidence, suggests a role for these enzymes in growth or cell cycle control. ..
- Avraham E, Szargel R, Eyal A, Rott R, Engelender S. Glycogen synthase kinase 3beta modulates synphilin-1 ubiquitylation and cellular inclusion formation by SIAH: implications for proteasomal function and Lewy body formation. J Biol Chem. 2005;280:42877-86 pubmed
- Xiang L, Gilkes D, Hu H, Takano N, Luo W, Lu H, et al. Hypoxia-inducible factor 1 mediates TAZ expression and nuclear localization to induce the breast cancer stem cell phenotype. Oncotarget. 2014;5:12509-27 pubmed..Second, HIF-1 activates transcription of the SIAH1 gene, which encodes a ubiquitin protein ligase that is required for the hypoxia-induced ubiquitination and ..
- Bursen A, Moritz S, Gaussmann A, Moritz S, Dingermann T, Marschalek R. Interaction of AF4 wild-type and AF4.MLL fusion protein with SIAH proteins: indication for t(4;11) pathobiology?. Oncogene. 2004;23:6237-49 pubmed..MLL fusion protein. The underlying oncogenic mechanism involves the two E3 ubiquitin ligases SIAH1 and SIAH2, the N-terminal portion of AF4 and the protection of the AF4...
- Suarez S, McCollum G, Jayagopal A, Penn J. High Glucose-induced Retinal Pericyte Apoptosis Depends on Association of GAPDH and Siah1. J Biol Chem. 2015;290:28311-20 pubmed publisher..the interaction between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the E3 ubiquitin ligase, seven in absentia homolog 1 (Siah1), was recently identified in ocular tissues...
- Zhang Q, Wang Z, Hou F, Harding R, Huang X, Dong A, et al. The substrate binding domains of human SIAH E3 ubiquitin ligases are now crystal clear. Biochim Biophys Acta Gen Subj. 2017;1861:3095-3105 pubmed publisher..b>SIAH1 and SIAH2 have been found to function as a tumour repressor and a proto-oncogene, respectively, despite the high ..
- Davies G, Ettenberg S, Coats A, Mussante M, Ravichandran S, Collins J, et al. Cbl-b interacts with ubiquitinated proteins; differential functions of the UBA domains of c-Cbl and Cbl-b. Oncogene. 2004;23:7104-15 pubmed..This in vivo result is consistent with the differences in ubiquitin binding observed in vitro between the UBAb and UBAc. This difference in ubiquitin-binding may reflect distinct regulatory functions of c-Cbl and Cbl-b. ..
- Kim H, Jeong W, Ahn K, Ahn C, Kang S. Siah-1 interacts with the intracellular region of polycystin-1 and affects its stability via the ubiquitin-proteasome pathway. J Am Soc Nephrol. 2004;15:2042-9 pubmed..These results suggest that polycystin-1 is regulated by Siah-1 through the ubiquitin-dependent proteasome pathway. ..
- Miura H, Hashida K, Sudo H, Awa Y, Takarada Iemata M, Kokame K, et al. Deletion of Herp facilitates degradation of cytosolic proteins. Genes Cells. 2010;15:843-53 pubmed publisher..Herp temporarily bound to alpha-synuclein, synphilin-1 and the E3 ligase SIAH1a during proteolytic stress but not during ER stress...
- Relaix F, Wei X, Li W, Pan J, Lin Y, Bowtell D, et al. Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis. Proc Natl Acad Sci U S A. 2000;97:2105-10 pubmed..induction of Pw1/Peg3 depends on p53 activity, we show that Pw1/Peg3 interacts with a p53-inducible gene product Siah1a. We demonstrate that coexpression of Pw1/Peg3 with Siah1a induces apoptosis independently of p53 whereas ..
- Tristan C, Ramos A, Shahani N, Emiliani F, Nakajima H, Noeh C, et al. Role of apoptosis signal-regulating kinase 1 (ASK1) as an activator of the GAPDH-Siah1 stress-signaling cascade. J Biol Chem. 2015;290:56-64 pubmed publisher..GAPDH) plays roles in both energy maintenance, and stress signaling by forming a protein complex with seven in absentia homolog 1 (Siah1)...
- Aga M, Kondo S, Wakisaka N, Moriyama Kita M, Endo K, Nakanishi Y, et al. Siah-1 is associated with expression of hypoxia-inducible factor-1α in oral squamous cell carcinoma. Auris Nasus Larynx. 2017;44:213-219 pubmed publisher..001). These results suggested that the expressions of Siah-1 and HIF-1α were clearly correlated in OSCC. Moreover, Siah-1 appears to be correlated with clinicopathological data, particularly tumor size. ..
- Wu H, Lin Y, Shi Y, Qian W, Tian Z, Yu Y, et al. SIAH-1 interacts with mammalian polyhomeotic homologues HPH2 and affects its stability via the ubiquitin-proteasome pathway. Biochem Biophys Res Commun. 2010;397:391-6 pubmed publisher..Thus, our results propose a novel role of SIAH-1 in regulating the expression level of HPH2 through the ubiquitin-proteasome pathway. ..