E2FBP1/DRIL1, an AT-rich interaction domain-family transcription factor, is regulated by p53.

E2FBP1/DRIL1 is an AT-rich interaction domain DNA-binding protein and is ubiquitously expressed in various tissues. It has been shown that Bright, the mouse orthologue of E2FBP1/DRIL1, exhibits sequence-specific DNA binding and regulates immunoglobulin transcription. Here we show a novel connection between E2FBP1/DRIL1 and the p53 tumor suppressor, a key regulator of growth arrest or apoptosis in response to cellular stress. We found a putative p53-binding site, which specifically responded to p53, in the second intron of the E2FBP1/DRIL1 gene. E2FBP1/DRIL1was induced by p53 and up-regulated following DNA damage caused by UV radiation or doxorubicin treatment in a manner dependent on endogenous p53. The ectopic expression of E2FBP1/DRIL1 induced growth arrest in U2OS cells expressing normal p53, but not Saos-2 cells lacking p53. These results suggest that E2FBP1/DRIL1 may play a role in growth suppression mediated by p53.

[1]  G. Daley,et al.  A functional screen identifies hDRIL1 as an oncogene that rescues RAS-induced senescence , 2002, Nature Cell Biology.

[2]  Yusuke Nakamura,et al.  Cyclin K as a direct transcriptional target of the p53 tumor suppressor. , 2002, Neoplasia.

[3]  Y Taya,et al.  p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis. , 2001, Molecular cell.

[4]  R. Scheuermann,et al.  Transcriptional Activation by a Matrix Associating Region-binding Protein , 2001, The Journal of Biological Chemistry.

[5]  A. Levine,et al.  Surfing the p53 network , 2000, Nature.

[6]  P. Pandolfi,et al.  Regulation of p53 activity in nuclear bodies by a specific PML isoform , 2000, The EMBO journal.

[7]  Ailan Guo,et al.  The function of PML in p53-dependent apoptosis , 2000, Nature Cell Biology.

[8]  Yusuke Nakamura,et al.  p53AIP1, a Potential Mediator of p53-Dependent Apoptosis, and Its Regulation by Ser-46-Phosphorylated p53 , 2000, Cell.

[9]  P. Tucker,et al.  Regulation of matrix attachment region‐dependent, lymphocyte‐restricted transcription through differential localization within promyelocytic leukemia nuclear bodies , 2000, The EMBO journal.

[10]  R. Saint,et al.  ARID proteins come in from the desert. , 2000, Trends in biochemical sciences.

[11]  Yusuke Nakamura,et al.  A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage , 2000, Nature.

[12]  Goberdhan P Dimri,et al.  Regulation of a Senescence Checkpoint Response by the E2F1 Transcription Factor and p14ARF Tumor Suppressor , 2000, Molecular and Cellular Biology.

[13]  J. Levine,et al.  Surfing the p53 network , 2000, Nature.

[14]  R. Saint,et al.  The Drosophila dead ringer gene is required for early embryonic patterning through regulation of argos and buttonhead expression. , 1999, Development.

[15]  A. Courey,et al.  Dorsal-Mediated Repression Requires the Formation of a Multiprotein Repression Complex at the Ventral Silencer , 1998, Molecular and Cellular Biology.

[16]  S. Sekiya,et al.  A novel E2F binding protein with Myc-type HLH motif stimulates E2F-dependent transcription by forming a heterodimer , 1998, Oncogene.

[17]  R. Saint,et al.  The human dead ringer/bright homolog, DRIL1: cDNA cloning, gene structure, and mapping to D19S886, a marker on 19p13.3 that is strictly linked to the Peutz-Jeghers syndrome. , 1998, Genomics.

[18]  C. Webb,et al.  Expression of bright at two distinct stages of B lymphocyte development. , 1998, Journal of immunology.

[19]  W. El-Deiry,et al.  Regulation of p53 downstream genes. , 1998, Seminars in cancer biology.

[20]  S. Lowe,et al.  Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a , 1997, Cell.

[21]  J. Nevins,et al.  Functional analysis of E2F transcription factor. , 1997, Methods in enzymology.

[22]  K. Kinzler,et al.  Genetic determinants of p53-induced apoptosis and growth arrest. , 1996, Genes & development.

[23]  C. Prives,et al.  p53: puzzle and paradigm. , 1996, Genes & development.

[24]  J. Nevins,et al.  A unique role for the Rb protein in controlling E2F accumulation during cell growth and differentiation. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[25]  R. Saint,et al.  Characterization of the dead ringer gene identifies a novel, highly conserved family of sequence-specific DNA-binding proteins , 1996, Molecular and cellular biology.

[26]  Y. Kanegae,et al.  Efficient generation of recombinant adenoviruses using adenovirus DNA-terminal protein complex and a cosmid bearing the full-length virus genome. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[27]  R. Scheuermann,et al.  The immunoglobulin heavy-chain matrix-associating regions are bound by Bright: a B cell-specific trans-activator that describes a new DNA-binding protein family. , 1995, Genes & development.

[28]  J. Nevins,et al.  Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes , 1995, Molecular and cellular biology.

[29]  David Beach,et al.  p21 is a universal inhibitor of cyclin kinases , 1993, Nature.

[30]  J. Trent,et al.  WAF1, a potential mediator of p53 tumor suppression , 1993, Cell.

[31]  S. Elledge,et al.  The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases , 1993, Cell.