SEI family of nuclear factors regulates p53-dependent transcriptional activation.
SEI family proteins, p34SEI-1 and SEI-2(TRIP-Br2), are nuclear factors that are implicated in cell cycle regulation through interaction with CDK4/CyclinD and E2F-1/DP-1 complexes. Here we report that the SEI family proteins regulate transcriptional activity of p53 tumor suppressor protein. Expression of SEI-1, SEI-2 or SEI-3 strongly stimulates p53-dependent gene activation in HeLa and U2OS cells but not in p53-deficient Saos2 or p53-knockdown HeLa cells. SEI proteins possess an intrinsic transactivation activity, interact with the coactivator CREB-binding protein, and cooperate synergistically with the ING family of chromatin-associated proteins to stimulate the transactivation function of p53. Doxycycline-induced expression of SEI proteins results in activation of the p21 gene and inhibition of cell growth, but the growth arrest was not suppressed by the siRNA-mediated knockdown of the endogenous p53 protein. These results indicate that the SEI family of nuclear proteins regulates p53 transcriptional activity and a p53-independent signaling pathway leading to growth inhibition.
Watanabe-Fukunaga
Rie
R
Department of Genetics, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Iida
Satoshi
S
Shimizu
Yusuke
Y
Nagata
Shigekazu
S
Fukunaga
Rikiro
R
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D018929:Cell Culture Techniques; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002843:Chromatin; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013045:Species Specificity; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D002843:Chromatin; D008565:Membrane Proteins; D009687:Nuclear Proteins; C498710:PAG1 protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; C402464:SERTAD1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53