ArticleMolecular and cellular biology2007
Cdh1-anaphase-promoting complex targets Skp2 for destruction in transforming growth factor beta-induced growth inhibition.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
- Role of Cyclins and Cytoskeletal Proteins in Endometriosis: Insights into Pathophysiology.Cancers · 2024Review
- Depletion of DNA damage binding protein 2 sensitizes triple-negative breast cancer cells to poly ADP-ribose polymerase inhibition by destabilizing Rad51.Cancer science · 2019Article
- 14-3-3ζ targeting induced senescence in Hep-2 laryngeal cancer cell through deneddylation of Cullin1 in the Skp1-Cullin-F-box protein complex.Cell proliferation · 2019Article
- Mechanisms for the temporal regulation of substrate ubiquitination by the anaphase-promoting complex/cyclosome.Cell division · 2019Review
- APC/CCellular and molecular life sciences : CMLS · 2019Article
- SKP2 Activation by Thyroid Hormone Receptor β2 Bypasses Rb-Dependent Proliferation in Rb-Deficient Cells.Cancer research · 2017Article
- The β-TrCP-FBXW2-SKP2 axis regulates lung cancer cell growth with FBXW2 acting as a tumour suppressor.Nature communications · 2017Article
- Activation of anaphase-promoting complex by p53 induces a state of dormancy in cancer cells against chemotherapeutic stress.Oncotarget · 2016Article
- TGF-β activates APC through Cdh1 binding for Cks1 and Skp2 proteasomal destruction stabilizing p27kip1 for normal endometrial growth.Cell cycle (Georgetown, Tex.) · 2016Article
- The control operated by the cell cycle machinery on MEF2 stability contributes to the downregulation of CDKN1A and entry into S phase.Molecular and cellular biology · 2015Article
- Effect of cilostazol pretreatment on the PARP/AIF-mediated apoptotic pathway in rat cerebral ischemia-reperfusion models.Experimental and therapeutic medicine · 2014Article
- Roles of the Skp2/p27 axis in the progression of chronic nephropathy.Cellular and molecular life sciences : CMLS · 2013Review
- Regulation of APC/C-Cdh1 and its function in neuronal survival.Molecular neurobiology · 2012Review
- Novel insight into KLF4 proteolytic regulation in estrogen receptor signaling and breast carcinogenesis.The Journal of biological chemistry · 2012Article
- The retinoblastoma family of proteins and their regulatory functions in the mammalian cell division cycle.Cell division · 2012Article
- The emerging role of APC/CCdh1 in development.Seminars in cell & developmental biology · 2011Review
- Phosphorylation of the anaphase-promoting complex/Cdc27 is involved in TGF-beta signaling.The Journal of biological chemistry · 2011Article
- Regulation of Krüppel-like factor 4 by the anaphase promoting complex pathway is involved in TGF-beta signaling.The Journal of biological chemistry · 2011Article
- Nuclear translocation of Skp2 facilitates its destruction in response to TGFβ signaling.Cell cycle (Georgetown, Tex.) · 2011Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
As a subunit of a ubiquitin ligase, Skp2 is implicated in facilitating cell cycle progression via degradation of various protein targets. We report here that Skp2 is rapidly degraded following cellular stimulation by the cytokine transforming growth factor beta (TGF-beta) and that this degradation stabilizes the cell cycle arrest protein p27. The Skp2 degradation is mediated by Cdh1-anaphase-promoting complex (APC), as shown by depletion of Cdh1 with small interfering RNA, and by reconstitution of ubiquitylation reactions in a purified system. Blockage of Skp2 degradation greatly reduces TGF-beta-induced cell cycle arrest, as does expression of a nondegradable Skp2 mutant. Furthermore, we demonstrate that TGF-beta-induced Skp2 degradation is mediated by the Smad cascade. The degradation of Skp2 stabilizes p27, thereby ensuring TGF-beta-induced cell cycle arrest. These results identify a novel mechanism for tumor suppression by TGF-beta and explain why dysfunction of APC in the TGF-beta pathway in responsive cells is associated with cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.