Document Detail

Restoration of the tumor suppressor p53 by downregulating cyclin B1 in human papillomavirus 16/18-infected cancer cells.
MedLine Citation:
PMID:  20661218     Owner:  NLM     Status:  In-Process    
Abrogation of functional p53 is responsible for malignant cell transformation and the maintenance of malignant state of human papillomavirus-infected cancer cells. Thus, restoration of p53 has been regarded as an important strategy for molecular intervention combating papillomavirus-associated malignancies. We show here that depleting cyclin B1 stabilizes and reactivates p53 in papillomavirus-infected cervical cancer cell lines HeLa and CaSki. HeLa cells depleted of cyclin B1 exhibit mitotic defects in spindle formation and chromosome alignment. Downregulation of cyclin B1 increases p14 alternative reading frame of p16, the positive regulator of p53, and decreases phosphorylation of Ser315 in p53. Whereas RO-3306, a selective inhibitor of cyclin-dependent kinase 1 (Cdk1), suppresses this phosphorylation at Ser315 of p53, ZM447439, targeting Aurora A/B kinases, shows no effect. Further analyses in HeLa cells and HCT116 p53(-/-) cells suggest that the Ser315 phosphorylation by Cdk1 regulates negatively the protein stability and the function of p53. Moreover, increased p53 in HeLa cells is functional by showing its increased downstream effectors p21, mouse double minute 2 and Bax. Restoration of p53 and silencing cyclin B1 render cervical carcinoma cells more susceptible to DNA damage agent camptothecin. Taken together, targeting cyclin B1 might be an attractive strategy for preventing and treating papillomavirus-associated cancer by reactivating p53 and by reducing the Cdk1 activity.
N N Kreis; M Sanhaji; A Krämer; K Sommer; F Rödel; K Strebhardt; J Yuan
Related Documents :
12534338 - Further characterization of bc3h1 myogenic cells reveals lack of p53 activity and under...
19020758 - Proton induces apoptosis of hypoxic tumor cells by the p53-dependent and p38/jnk mapk s...
7798388 - Altered p53 expression and epidermal cell proliferation is seen in vulval lichen sclero...
19513548 - Axin induces cell death and reduces cell proliferation in astrocytoma by activating the...
7315338 - Tumours in iceland. 3. malignant tumours of kidney. a histological classification.
2858858 - The change from symmetry to asymmetry of a sodium transport system in red cell membranes.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-26
Journal Detail:
Title:  Oncogene     Volume:  29     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  5591-603     Citation Subset:  IM    
Department of Gynecology and Obstetrics, School of Medicine, JW Goethe University, Frankfurt, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  The inhibition of Bid expression by Akt leads to resistance to TRAIL-induced apoptosis in ovarian ca...
Next Document:  Extracellular adenosine triphosphate and adenosine in cancer.