Human Parvovirus B19 nonstructural protein transactivates the p21/WAF1 through Sp1.
The expression of human Parvovirus B19 nonstructural protein 1 (NS1) induces cell cycle arrest at the G1 phase and is accompanied by increased expression of the cyclin-dependent kinase inhibitor, p21/WAF1. Here, we provide direct evidence that NS1 mediates the transactivation of p21/WAF1. Up-regulation of p21/WAF1 by wild-type NS1 but not an NS1 mutant deleted of its NTP binding motif was observed. We also demonstrated that the wild-type NS1 is unable to induce G1 arrest in p21-deficient cells. Using reporter plasmids containing various mutants of the p21/WAF1 promoter, luciferase assay further revealed that the binding sites of the promoter to the transcription factor Sp1 are critical for NS1-mediated transactivation. Indeed Sp1 interacts only with the wild-type NS1 but not the NS1 mutant. These results indicate a cooperative contribution of NS1 and Sp1 to the transactivation of p21/WAF1, which leads to G1 arrest.
Nakashima
Akitoshi
A
Department of Microbiology and Immunology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8575, Japan.
Morita
Eiji
E
Saito
Shigeru
S
Sugamura
Kazuo
K
D001483:Base Sequence; D001665:Binding Sites; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016193:G1 Phase; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016732:Parvovirus B19, Human / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; C106202:NS1 protein, parvovirus; D016329:Sp1 Transcription Factor; D017361:Viral Nonstructural Proteins