DEN1(15q23) SENP8, deneddylaasi, NEDD8-spesifinen sumopeptidaasiperheen jäsen

https://www.ncbi.nlm.nih.gov/gene/123228

SENP8 provided by HGNC

Official Full Name

SUMO peptidase family member, NEDD8 specific provided by HGNC

Also known as

DEN1; NEDP1; PRSC2

Summary

This gene encodes a cysteine protease that is a member of the sentrin-specific protease family. The encoded protein is involved in processing and deconjugation of the ubiquitin-like (UBL) protein termed, neural precursor cell expressed developmentally downregulated 8 (NEDD8). Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

Expression

Broad expression in testis (RPKM 2.2), thyroid (RPKM 1.6) and 23 other tissues See more

Orthologs

mouse all

  

Related articles in PubMed

1. The molecular determinants of NEDD8 specific recognition by human SENP8. Shin YC, et al. PLoS One, 2011. PMID 22110750, Free PMC Article
2. DeSUMOylating enzymes--SENPs. Drag M, et al. IUBMB Life, 2008 Nov. PMID 18666185
3. Central role for endothelial human deneddylase-1/SENP8 in fine-tuning the vascular inflammatory response. Ehrentraut SF, et al. J Immunol, 2013 Jan 1. PMID 23209320, Free PMC Article
4. A time-resolved fluorescence resonance energy transfer-based assay for DEN1 peptidase activity. Engels IH, et al. Anal Biochem, 2009 Jul 1. PMID 19328766
5. Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1. Shen LN, et al. EMBO J, 2005 Apr 6. PMID 15775960, Free PMC Article

See all (33) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

 

GeneRIFs: Gene References Into Functions

1. Impairment of NEDDylation by Ubc12 knockout enhances PCNA ubiquitination and promotes PCNA-poleta interaction, while up-regulation of NEDDylation by NEDD8 overexpression or NEDP1 deletion reduces the excessive accumulation of ubiquitinated PCNA. Moreover, Ubc12 knockout decreases cell sensitivity to H2O2-induced oxidative stress, but NEDP1 deletion aggravates this sensitivity
2. Furthermore, the authors characterized SENP8/DEN1 as the protease that counteracts Ubc12 auto-neddylation, and observed aberrant neddylation of Ubc12 and other NEDD8 conjugation pathway components in SENP8-deficient cells.
3. In endothelial dysfunction, HDAC2 levels were reciprocally regulated by ectopic expression of NEDD8 and the de-NEDDylating enzyme SENP8.
4. the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype.Small Ubiquitin–like MOdifier (SUMO) proteins are small protein modifiers capable of regulating cellular localization and function of target proteins. Over the last few years, a relevant role has been demonstrated for sumoylation in the modulation of important cellular processes, including gene transcription, DNA repair, cell-cycle regulation and apoptosis. Components of the sumoylation machinery have been found deregulated in different human cancers, and are thought to significantly affect cancer cell progression. In the present study we sought to analyze the expression of all the components of the sumoylation machinery in a case study comprising 77 papillary thyroid cancers (PTC) and normal matched tissues. In particular, we evaluated the expression of the SENP1 to SENP8 (SENtrin-specific proteases), SAE1 (SUMO1 activating enzyme subunit 1), UBA2 (UBiquitin-like modifier activating enzyme 2), UBC9 (UBiquitin conjugating enzyme 9), RanBP2 (RAN binding protein 2), MSMCE2 (Non- SMC element 2), CBX4 (ChromoBoX homolog 4), PIAS1 to PIAS4 (protein inhibitor of activated STAT), ZMIZ1 (zinc finger, MIZ-type containing 1) and ZMIZ2 (Zinc finger, MIZ-type containing 2) by means of quantitative RT-PCR. In most of the PTC examined we observed a significant alteration in the mRNAs of SENP8, ZMIZ1, SAE1, PIAS1 and PIAS2. These tended to be reduced in about 50 to 66% of cases, and unchanged or increased in the remaining ones. Univariate and Kaplan-Mayer analyses documented the lack of association between the expression of the above 5 genes and clinicopathological parameters. Only SAE1 was significantly higher in female PTC tissues, in respect to male PTC tissues (p=0.021), and SENP8 was significantly lower in TNM stages III-V, with respect to stages I-II (p=0.047). In conclusion, we demonstrated that the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype. However, differently from other human cancers, their mRNA level does not represent a prognostic biomarker in PTC patients.
5. Data indicate that overexpression of SENP8, a NEDD8-specific cysteine protease, resulted in deNEDDylation of E2F1 and promoted its transactivation activity at the p73 gene.
6. We analyzed whether CSN1 alone can increase DEN1 degradation in HeLa cells.these data suggest that the COP9 signalosome supports proteasome-dependent protein degradation of DEN1/DenA in fungi and in human cells.The CSN-DEN1/DenA interaction that affects DEN1/DenA protein levels presumably balances cellular deneddylase activity. A deneddylase disequilibrium impairs multicellular development and suggests that control of deneddylase activity is important for multicellular development.
7. A role for SENP8 as a central regulator of the inflammatory process is identified using knockdown and overexpression approaches.
8. the specificity of NEDD8-specific peptidase SENP8
9. Data show that the stability of MDM2 is regulated by NEDD8 pathway and identify NEDP1 that deneddylates MDM2, resulting in MDM2 destabilization concomitant with p53 activation.
10. NEDP1 is likely to play an important role in ubiquitin-mediated proteolysis by controlling the activity of SCF complexes

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