Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SUMO conjugation emerges as an important mechanism in regulating protein localization, stability and activity. SUMOylation is a dynamic process and can be reversed by a family of sentrin/SUMO-specific proteases (SENPs). However, the biological roles of SENPs in cellular processes are largely unknown. Here, we show that SENP1, a member of SENP family, is overexpressed in most of colon cancer tissues. Silencing of SENP1 expression inhibits cell growth with G(1) arrest in vitro and in nude mice and colony formation in colon cancer cell line DLD-1, suggesting that SENP1 is essential for cell growth in the colon cancer cell line. Accordingly, silencing of SENP1 results in upregulation of CDK inhibitors such as p16, p19, p21 and p27. These results suggest that SENP1 might play a role in cell cycle regulation of colon cancer cells.
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PMID:SUMO-specific protease 1 regulates the in vitro and in vivo growth of colon cancer cells with the upregulated expression of CDK inhibitors. 2166 91

SUMO-specific protease 2 (SENP2) activities to remove SUMO from its substrates is essential for development of trophoblast stem cells, niches and lineages. Global deletion of SENP2 leads to midgestation lethality, and causes severe defects in the placenta which is accompanied by embryonic brain and heart abnormalities. Because of the placental deficiencies, the role of SENP2 in development of the embryonic tissues has not been properly determined. The brain and heart abnormalities may be secondary to placental insufficiency. Here we have created a new mouse strain permitting conditional inactivation of SENP2. Mice homozygous for germline deletion of the conditional allele exhibit trophoblast defects and embryonic abnormalities resembling the global SENP2 knockout. However, tissue-specific disruptions of SENP2 demonstrate its dispensable role in embryogenesis. Placental expression of SENP2 is necessary and sufficient for embryonic heart and brain development. Using a protease deficient model, we further demonstrate the requirement of SENP2-dependent SUMO modification in development of all major trophoblast lineages. SENP2 regulates sumoylation of Mdm2 which controls p53 activities critical for G-S transition of mitotic division and endoreduplication in trophoblast proliferation and differentiation, respectively. The differentiation of trophoblasts is also dependent on SENP2-mediated activation of p57(Kip2), a CDK-specific inhibitor required for endoreduplication.
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PMID:Extraembryonic but not embryonic SUMO-specific protease 2 is required for heart development. 2688 97

We previously showed that p21Cip1 transits through the nucleolus on its way from the nucleus to the cytoplasm and that DNA damage inhibits this transit and induces the formation of p21Cip1-containing intranucleolar bodies (INoBs). Here, we demonstrate that these INoBs also contain SUMO-1 and UBC9, the E2 SUMO-conjugating enzyme. Furthermore, whereas wild type SUMO-1 localized in INoBs, a SUMO-1 mutant, which is unable to conjugate with proteins, does not, suggesting the presence of SUMOylated proteins at INoBs. Moreover, depletion of the SUMO-conjugating enzyme UBC9 or the sumo hydrolase SENP2 changed p21Cip1 intracellular distribution. In addition to SUMO-1 and p21Cip1, cell cycle regulators and DNA damage checkpoint proteins, including Cdk2, Cyclin E, PCNA, p53 and Mdm2, and PML were also detected in INoBs. Importantly, depletion of UBC9 or p21Cip1 impacted INoB biogenesis and the nucleolar accumulation of the cell cycle regulators and DNA damage checkpoint proteins following DNA damage. The impact of p21Cip1 and SUMO-1 on the accumulation of proteins in INoBs extends also to CRM1, a nuclear exportin that is also important for protein translocation from the cytoplasm to the nucleolus. Thus, SUMO and p21Cip1 regulate the transit of proteins through the nucleolus, and that disruption of nucleolar export by DNA damage induces SUMO and p21Cip1 to act as hub proteins to form a multiprotein complex in the nucleolus.
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PMID:SUMO regulates p21Cip1 intracellular distribution and with p21Cip1 facilitates multiprotein complex formation in the nucleolus upon DNA damage. 2858 71

Dysregulation of SUMO-specific protease 1 (SENP1) expression has been reported in several kinds of cancer, including human colorectal and prostate cancers, proposing SENP1 as an oncogene with a critical role in cancer progression. miR-133a-3p has been reported as a tumor suppressor in several malignant neoplasias. However, the precise molecular mechanisms underlying its role in colorectal cancer remain largely unknown. The aim of this work was to investigate the relationship between miR-133a-3p and SENP1 in colorectal cancer cells. We found that miR-133a-3p expression was downregulated in colorectal cancer tissues. In silico analyses indicated that SENP1 is one of the target genes of miR-133a-3p. Overexpression of miR-133a-3p mimics was able to inhibit cell growth with G1 arrest of colorectal cancer cells. Overexpression of miR-133a-3p antisense promoted cell growth of colorectal cancer cells. The luciferase reporter experiments showed that miR-133a-3p regulated the expression of SENP1 by combining with its 3'-UTR and resulted in downregulation of SENP1 and upregulation of CDK inhibitors such as p16, p19, p21, and p27. These results suggest that the miR-133a-3p-SENP1 axis might play a role in cell proliferation and cell cycle regulation of colorectal cancer cells.
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PMID:miR-133a-3p Targets SUMO-Specific Protease 1 to Inhibit Cell Proliferation and Cell Cycle Progress in Colorectal Cancer. 2874 80