SEI family of nuclear factors regulates p53-dependent transcriptional activation

Genes Cells. 2005 Aug;10(8):851-60. doi: 10.1111/j.1365-2443.2005.00881.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Cell Culture Techniques
  • Cell Cycle
  • Cell Cycle Proteins
  • Chromatin
  • HeLa Cells
  • Humans
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / metabolism
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Species Specificity
  • Time Factors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / metabolism*
  • Two-Hybrid System Techniques


  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Chromatin
  • Membrane Proteins
  • Nuclear Proteins
  • PAG1 protein, human
  • Phosphoproteins
  • RNA, Messenger
  • SERTAD1 protein, human
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Protein p53