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General Comment |
The ubiquitin-specific protease USP34 regulates axin stability and Wnt/β-catenin signaling. Lui TT et al. (2011) Wnt proteins control multiple cell behaviors during development and tissue homeostasis. However, pathological activation of Wnt signaling is the underlying cause of various human diseases. The ubiquitin-proteasome system plays important regulatory functions within the Wnt pathway by regulating the activity of several of its core components. Hence, multiple E3 ubiquitin ligases have been implicated in its regulation. Less is known, however, about the role of ubiquitin-specific proteases in Wnt signaling. Analysis of purified axin-containing protein complexes by liquid chromatography-tandem mass spectrometry revealed the presence of the ubiquitin protease USP34. Our results indicate that USP34 functions downstream of the β-catenin destruction complex to control the stability of axin and opposes its tankyrase-dependent ubiquitination. Reflecting on the requirement for tight control of axin homeostasis during Wnt signaling, interfering with USP34 function by RNA interference leads to the degradation of axin and to the inhibition of β-catenin-mediated transcription. Given the numerous human diseases exhibiting spurious Wnt pathway activation, the development of USP34 inhibitors may offer a novel therapeutic opportunity.//////////////////
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Mutations |
1 mutations
Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: An association study between USP34 and polycystic ovary syndrome. Zhao S et al. (2015) Polycystic ovary syndrome (PCOS) is a complex multifactor disorder and genetic factors have been implicated in its pathogenesis. Our previous genome-wide association study (GWAS) had identified allele frequencies in several single nucleotide polymorphisms (SNPs) in gene USP34 (Ubiquitin-Specific Protease 34) were significantly different between PCOS cases and controls. This study was aimed to replicate the previous results in another independent cohort. One thousand two hundred eighteen PCOS cases and 1057 controls were recruited. Genotyping of two SNPs (rs17008097 and rs17008940) in USP34 gene were performed by TaqMan-MGB probe assay and genotype-phenotype analysis was conducted subsequently. The differences of allele or genotype frequencies were not significant statistically between PCOS and controls, even after age and BMI adjustment. For clinical and metabolic features (LH, T and HOMA-IR) analysis in PCOS cases, no statistical differences among three genotypes of rs17008097 and rs17008940 were found. However, rs17008940 was shown to be slightly associated with BMI in PCOS cases rather than in controls, even after age adjustment (TC vs CC P = 0.006, OR = 1.042, 95% CI 1.012-1.073; TT vs CC P = 0.037, OR = 1.050, 95% CI 1.003-1.100). USP34 gene polymorphisms (rs17008097 and rs17008940) may not be associated with PCOS in the Han Chinese women.//////////////////
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