Inhibition of F-Box protein p45(SKP2) expression and stabilization of cyclin-dependent kinase inhibitor p27(KIP1) in vitamin D analog-treated cancer cells

Endocrinology
R LinJ H White

Abstract

Treatment of cancer cells with 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D(3)] or its analogs induces growth arrest and expression of the cyclin-dependent kinase inhibitor p27(KIP1). Although 1,25(OH)(2)D(3) transiently enhances p27(kip1) gene transcription in some cells, its effects on p27(KIP1) protein levels are generally more gradual and sustained. This suggests that 1,25(OH)(2)D(3) treatment may be stabilizing p27(KIP1) protein, which is sensitive to modification by the SCF(SKP2) protein ubiquitin ligase and proteosomal degradation. Here, we show that treatment of AT-84 head and neck squamous carcinoma cells with the 1,25(OH)(2)D(3) analog EB1089 increases p27(KIP1) protein levels without significantly affecting expression of its mRNA. EB1089 treatment repressed expression of mRNAs encoding the F-box protein p45(SKP2), a marker of poor head and neck cancer prognosis, and the cyclin kinase subunit CKS1, which is essential for targeting p45(SKP2) to p27(KIP1). This coincided with a reduction of total p45(SKP2) protein, and p45(SKP2) associated with p27(KIP1). Consistent with these findings, turnover of p27(KIP1) protein was strongly inhibited in the presence of EB1089. A similar reduction in p45(SKP2) expression and stabilization...Continue Reading

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Citations

Nov 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Reyhaneh Salehi-TabarJohn H White
Aug 25, 2010·Molecular and Cellular Biology·Beum-Soo AnJohn H White
Jul 21, 2006·Biogerontology·Verónica Gonzalez PardoAna Russo de Boland
Aug 15, 2013·Critical Reviews in Oncology/hematology·Michelino Di RosaLucia Malaguarnera
May 19, 2009·Critical Reviews in Oncology/hematology·Khanh vinh quoc Luong, Lan Thi Hoang Nguyen
Sep 23, 2008·The International Journal of Biochemistry & Cell Biology·James L ThorneBryan M Turner
Apr 23, 2009·Journal of Cellular and Molecular Medicine·Darja ObradovicTheo Rein
Aug 22, 2006·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Claudia GedlickaMichael Formanek
Jul 1, 2004·The Journal of Steroid Biochemistry and Molecular Biology·John H White
Feb 25, 2014·Journal of Cancer Therapy·Vinayak Khattar, Jaideep V Thottassery
Mar 31, 2009·Leukemia Research·Jing-Yi ChenWen-Chun Hung
Apr 26, 2011·The American Journal of Pathology·Arnaldo A ArbiniLoredana Moro
Dec 30, 2003·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Roberto Lin, John H White
Sep 4, 2003·The Journal of Biological Chemistry·You-Wei ZhangIkuo Morita
Mar 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Luz E Tavera-MendozaMyles Brown
May 2, 2006·Molecular Cancer Therapeutics·Sonoko Masuda, Glenville Jones
Dec 10, 2020·International Journal of Molecular Sciences·Sachin Bhoora, Rivak Punchoo

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