Document Detail


Cellular growth inhibition by FK778 is linked to G1 arrest or S phase accumulation, dependent on the functional status of the retinoblastoma protein.
MedLine Citation:
PMID:  19212661     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The malononitrilamide FK778 is a novel immunosuppressive agent with antiproliferative activities. To gain insight into the molecular mechanism of FK778-mediated growth inhibition, we analyzed cells which differ in their p53 status and functionality of retinoblastoma protein (pRb). FK778 acted as a broad inhibitor of cell proliferation independent of the p53 or pRb status. However, the mechanism of FK778-mediated growth inhibition differed, leading either to cell cycle arrest in G1, or cell accumulation in S phase. This differential response was linked to the phosphorylation status of pRb. In addition, since FK778 was reported to exhibit antiviral activities, we analyzed the effect of FK778 on the growth stimulatory human papillomavirus (HPV)-16 and -18 E7 genes. Although growth of HPV-positive cells was strongly inhibited by FK778, we did not observe significant effects on viral E7 expression, indicating that the antiproliferative effect is not linked to an antiviral activity of FK778.
Authors:
Karin Hoppe-Seyler; Kilian Weigand; Claudia Lohrey; Felix Hoppe-Seyler; Peter Sauer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  23     ISSN:  1107-3756     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-12     Completed Date:  2009-04-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  415-20     Citation Subset:  IM    
Affiliation:
Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg, Germany. k.hoppe-seyler@dkfz.de
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MeSH Terms
Descriptor/Qualifier:
Alkynes / pharmacology*
Antiviral Agents / pharmacology*
DNA-Binding Proteins / biosynthesis
G1 Phase / drug effects*
Hela Cells
Human papillomavirus 16 / metabolism
Human papillomavirus 18 / metabolism
Humans
Isoxazoles / pharmacology*
Nitriles / pharmacology*
Oncogene Proteins, Viral / biosynthesis
Phosphorylation / drug effects
Retinoblastoma Protein / metabolism*
S Phase / drug effects*
Tumor Suppressor Protein p53 / metabolism*
Chemical
Reg. No./Substance:
0/Alkynes; 0/Antiviral Agents; 0/DNA-Binding Proteins; 0/E7 protein, Human papillomavirus type 18; 0/Isoxazoles; 0/Nitriles; 0/Oncogene Proteins, Viral; 0/Retinoblastoma Protein; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/oncogene protein E7, Human papillomavirus type 16; 185915-33-7/2-cyano-3-hydroxy-N-(4-(trifluoromethyl)phenyl)-2-hepten-6-ynamide

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


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