The adenoviral E1A induces p21WAF1/CIP1 expression in cancer cells.
The adenovirus-5 E1A gene encodes two main proteins of 289 and 243 amino acid residues from 13S and 12S mRNA, respectively. The E1A gene products function as transcriptional regulators and have anti-tumor activities. Despite the fact that E1A gene therapy has been tested in clinical trials, the molecular mechanism by which it suppresses tumor cell growth is still not completely understood. Here, we show that E1A increases the expression of the cyclin-dependent kinase (CDK) inhibitor p21(WAF1/CIP1), which inhibits cell growth. We further show that 13S E1A, but not 12S E1A, can transactivate the p21 promoter through Sp1 sites. Interestingly, the E1A-induced transactivation occurs only in cancer cells, not in normal cells. This study provides new insight into the links between E1A and the CDK inhibitor and may have important clinical implications.
Najafi
S Mahmoud A
SM
Department of Molecular and Cellular Oncology, Box 108, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Li
Zheng
Z
Makino
Keishi
K
Shao
Ruping
R
Hung
Mien-Chie
MC
D017500:Adenovirus E1A Proteins / Q000494:pharmacology*; D001665:Binding Sites; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016329:Sp1 Transcription Factor