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Two distinct sites in Nup153 mediate interaction with the SUMO proteases SENP1 and SENP2.

ABSTRACT: Numerous enzymes of the mammalian SUMO modification pathway, including two members of the SUMO protease family, SENP2 and SENP1, localize to the nuclear periphery. The SUMO proteases play roles both in processing SUMO during the biogenesis of this peptide moiety and also in reversing SUMO modification on specific targets to control the activities conferred by this post-translational modification. Although interaction with the C-terminal domain of the nucleoporin Nup153 is thought to contribute to SENP2 localization at the nuclear pore complex, little is known about the binding partners of SENP1 at the nuclear periphery. We have found that Nup153 binds to both SENP1 and SENP2 and does so by interacting with the unique N-terminal domain of Nup153 as well as a specific region within the C-terminal FG-rich region. We have further found that Nup153 is a substrate for sumoylation, with this modification kept in check by these two SUMO proteases. Specifically, either RNAi depletion of SENP1/SENP2 or expression of dominantly interfering mutants of these proteins results in increased sumoylation of endogenous Nup153. While SENP1 and SENP2 share many characteristics, we show here that SENP1 levels are influenced by the presence of Nup153, whereas SENP2 is not sensitive to changes in Nup153 abundance.

SUBMITTER: Chow KH

PROVIDER: S-EPMC3679279 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Two distinct sites in Nup153 mediate interaction with the SUMO proteases SENP1 and SENP2.

Chow Kin-Hoe KH Elgort Suzanne S Dasso Mary M Ullman Katharine S KS

Nucleus (Austin, Tex.) 20120612 4

Numerous enzymes of the mammalian SUMO modification pathway, including two members of the SUMO protease family, SENP2 and SENP1, localize to the nuclear periphery. The SUMO proteases play roles both in processing SUMO during the biogenesis of this peptide moiety and also in reversing SUMO modification on specific targets to control the activities conferred by this post-translational modification. Although interaction with the C-terminal domain of the nucleoporin Nup153 is thought to contribute t ...[more]

PMID: 22688647

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Project description:SENP proteases take part in post-translational modification of proteins known as sumoylation. They catalyze three distinct processes during sumoylation: processing of SUMO protein, deconjugation of SUMO from the target protein, and chain editing which mentions to the dismantling of SUMO chain. Many proteins that are involved in the basic processes of cells, such as regulation of transcription, DNA repair or cell cycle control, are sumoylated. The aim of these studies was to investigate an association between polymorphic variants (SNPs) of the SENP1 gene (c.1691 + 36C > T, rs12297820) and SENP2 gene (c.902C > A, p.Thr301Lys, rs6762208) and a risk of breast cancer occurrence. We performed a case-control study in 324 breast cancer cases and 335 controls using PCR-RLFP. In the case of the SENP1 gene polymorphism we did not find any association between this polymorphism and breast cancer risk. In the case of SENP2 gene polymorphism we observed higher risk of breast cancer for carriers of the A allele (OR =1.33; 95 % CI 1.04-1.69). Our analysis also showed the genotype C/C (OR =0.67, 95 % CI 0.48-0.93) and the allele C (OR =0.75, 95 % CI 0.59-0.69) of this polymorphism decrease a risk of breast cancer. We also checked the distribution of genotypes and frequency of alleles of the SENP1 and SENP2 genes polymorphisms in groups of patients with different hormone receptor status, patients with positive and negative lymph node status and patients with different tumor grade. Odds ratio analysis showed a higher risk of metastases in women with the genotype C/C (OR =2.07, 95 % CI 1.06-4.05) and allele C (OR =2.10 95 % CI 1.10-4.01) of the c.1691 + 36C > T SENP1 gene polymorphism. Moreover, we observed reduced risk in women with the allele T (OR =0.48, 95 % CI 0.25-0.91) in this polymorphic site. In the case of SENP2 gene polymorphism we observed that the A/A genotype correlated with the lack of estrogen receptor (OR =1.94, 95 % CI 1.04-3.62). Our results suggest that the variability of the SENP1 and SENP2 genes may play a role in breast cancer occurrence. Further studies are needed to clarify their biological functions in breast cancer.

Dataset Information

Two distinct sites in Nup153 mediate interaction with the SUMO proteases SENP1 and SENP2.

Publications

Two distinct sites in Nup153 mediate interaction with the SUMO proteases SENP1 and SENP2.

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