ArticleProceedings of the National Academy of Sciences of the United States of America2006
Testing the importance of p27 degradation by the SCFskp2 pathway in murine models of lung and colon cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 64 citations in OpenAlex.
- Benzylguanine Induces Cellular Senescence and Decreases Relaxation of Vascular Smooth Muscle in the Rat Aorta.Archives of Razi Institute · 2025Article
- Distinct outcomes from targeted perturbations of the multi-subunit SCFCommunications biology · 2025Article
- Fatty Acid Synthase Promotes Hepatocellular Carcinoma Growth via S-Phase Kinase-Associated Protein 2/p27Medicina (Kaunas, Lithuania) · 2024Article
- Molecular profiling of colorectal cancer in a genetically admixed Hispanic population.Cancer medicine · 2023Article
- ZNF292 suppresses proliferation of ESCC cells through ZNF292/SKP2/P27 signaling axis.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2021Article
- Current Status of the Use of Multifunctional Enzymes as Anti-Cancer Drug Targets.Pharmaceutics · 2021Review
- Review
- Skp2-mediated ubiquitination and mitochondrial localization of Akt drive tumor growth and chemoresistance to cisplatin.Oncogene · 2019Article
- Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma.Journal of cell communication and signaling · 2019Article
- Binimetinib, a novel MEK1/2 inhibitor, exerts anti-leukemic effects under inactive status of PI3Kinase/Akt pathway.International journal of hematology · 2019Article
- Skp2 expression has different clinicopathological and prognostic implications in lung adenocarcinoma and squamous cell carcinoma.Oncology letters · 2018Article
- LTA4H regulates cell cycle and skin carcinogenesis.Carcinogenesis · 2017Article
- Deletion ofGut · 2017Article
- p27T187A knockin identifies Skp2/Cks1 pocket inhibitors for advanced prostate cancer.Oncogene · 2017Article
- p27kip1 expression limits H-Ras-driven transformation and tumorigenesis by both canonical and non-canonical mechanisms.Oncotarget · 2016Article
- Substituting threonine 187 with alanine in p27Kip1 prevents pituitary tumorigenesis by two-hit loss of Rb1 and enhances humoral immunity in old age.The Journal of biological chemistry · 2015Article
- The N-terminal region of p27 inhibits HIF-1α protein translation in ribosomal protein S6-dependent manner by regulating PHLPP-Ras-ERK-p90RSK axis.Cell death & disease · 2014Article
- A new tumour suppression mechanism by p27Kip1: EGFR down-regulation mediated by JNK/c-Jun pathway inhibition.The Biochemical journal · 2014Article
- Loss of p27 upregulates MnSOD in a STAT3-dependent manner, disrupts intracellular redox activity and enhances cell migration.Journal of cell science · 2014Article
- The ubiquitin proteasome system - implications for cell cycle control and the targeted treatment of cancer.Biochimica et biophysica acta · 2014Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Decreased expression of the CDK inhibitor p27kip1 in human tumors directly correlates with increased resistance to chemotherapies, increased rates of metastasis, and an overall increased rate of patient mortality. It is thought that decreased p27 expression in tumors is caused by increased proteasomal turnover, in particular activation of the pathway governed by the SCFskp2 E3 ubiquitin protein ligase. We have directly tested the importance of the SCFskp-mediated degradation of p27 in tumorigenesis by analyzing the tumor susceptibility of mice that express a form of p27 that cannot be ubiquitinated and degraded by this pathway (p27T187A). In mouse models of both lung and colon cancer down-regulation of p27 promotes tumorigenesis. However, we found that preventing p27 degradation by the SCFskp2 pathway had no impact on tumor incidence or overall survival in either tumor model. Our study unveiled a previously unrecognized role for the control of p27 mRNA abundance in the development of non-small cell lung cancers. In the colon cancer model, the frequency of intestinal adenomas was similarly unaffected by the p27T187A mutation, but, unexpectedly, we found that it inhibited progression of intestinal adenomas to carcinomas. These studies may guide the choice of clinical settings in which pharmacologic inhibitors of the Skp2 pathway might be of therapeutic value.
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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.