A novel mechanism for p53 to regulate its target gene ECK in signaling apoptosis

Details

• Personal Author:
  Brandt-Rauf PW ; Hei TK ; Jin YJ ; Qiao C ; Wang J ; Yin Y
• Description:
  Transcription factor p53 regulates its target genes through binding to DNA consensus sequence and activating the promoters of its downstream genes. The conventional p53 consensus binding sequence was defined as two copies of the 10-bp motif 5'-PuPuPuC(A/T)(T/A)GPyPyPy-3' with a spacer of 0 to 13 bp, which exists in the regulatory regions of some p53 target genes. However, there is no such p53 consensus sequence in the promoters of a number of p53-responsive genes, suggesting that there might be other mechanisms whereby p53 transactivates the promoters of its target genes. We report here that p53 uses a novel binding mechanism to regulate the transcription of epithelial cell kinase (ECK), a receptor protein-tyrosine kinase implicated in signal transduction. We show that p53 binds to a 10-bp perfect palindromic decanucleotide (GTGACGTCAC) in the ECK promoter, activates the ECK promoter, and increases the transcription of ECK. This palindrome is required for p53-mediated transactivation of the ECK promoter. ECK is highly responsive to oxidative damage that leads to cell death. Ectopic expression of ECK causes spontaneous apoptosis in breast cancer cells. We found that ectopic expression of a mutant ECK fails to induce apoptosis in cancer cells. Our findings show that p53 is a transcriptional regulator of ECK in mediating apoptosis. The discovery of the novel p53-binding motif in the promoter may lead to the identification of a new class of p53 target genes. [Description provided by NIOSH]
• Subjects:
  Amino Acids DNA Genetics Neoplasms Occupational Health Safety
• Keywords:
  Amino-acids Apoptosis Author Keywords: P53 Breast-cancer Cancer Cell-function DNA-damage ECK EphA2 Gene-mutation Genes Humans Molecular-biology Oxidative-processes Oxidative Stress Palindrome Protein-biochemistry Proteins Tumors

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• ISSN:
  1541-7786
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  4
• Issue:
  10
• NIOSHTIC Number:
  nn:20038418
• Citation:
  Mol Cancer Res 2006 Oct; 4(10):769-778
• Contact Point Address:
  Yuxin Yin, Department of Radiation Oncology College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA
• Email:
  yy151@columbia.edu
• Federal Fiscal Year:
  2007
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Performing Organization:
  Columbia University Health Sciences
• Peer Reviewed:
  True
• Start Date:
  20020601
• Source Full Name:
  Molecular Cancer Research
• End Date:
  20110630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b62e93fb830aebec54ee8346902d7f24d5a35dc477f87d4f6853bda082ffbff3858cc450fd5e7b0d1a5eb1ddbcd3fd0392513b4839ce82cf456b9c79e3fe280a
• Download URL:
  https://stacks.cdc.gov/view/cdc/192135/cdc_192135_DS1.pdf
• File Type:
  [PDF - 409.51 KB ]