Characterization of cells and gene-targeted mice deficient for the p53-binding kinase homeodomain-interacting protein kinase 1 (HIPK1)

Kondo, S., Lu, Y., Debbas, M., Lin, A. W., Sarosi, I., Itie, A., Wakeham, A., Tuan, J., Saris, C., Elliott, G., Ma, W. L., Benchimol, S., Lowe, S. W., Mak, T. W., Thukral, S. K. (April 2003) Characterization of cells and gene-targeted mice deficient for the p53-binding kinase homeodomain-interacting protein kinase 1 (HIPK1). Proceedings of the National Academy of Sciences of the United States of America, 100 (9). pp. 5431-5436. ISSN 0027-8424

URL: http://www.ncbi.nlm.nih.gov/pubmed/12702766
DOI: 10.1073/pnas.0530308100

Abstract

The tumor suppressor p53 is regulated in part by binding to cellular proteins. We used p53 as bait in the yeast two-hybrid system and isolated homeodomain-interacting protein kinase 1 (HIPK1) as a p53-binding protein. Deletion analysis showed that amino acids 100-370 of p53 and amino acids 885-1093 of HIPK1 were sufficient for HIPK1-p53 interaction. HIPK1 was capable of autophosphorylation and specific serine phosphorylation of p53. The HIPK1 gene was highly expressed in human breast cancer cell lines and oncogenically transformed mouse embryonic fibroblasts. HIPK1 was localized to human chromosome band 1p13, a site frequently altered in cancers. Gene-targeted HIPK1-/- mice were grossly normal but oncogenically transformed HIPK1-/- mouse embryonic fibroblasts exhibited reduced transcription of Mdm2 and were more susceptible than transformed HIPK1+/+ cells to apoptosis induced by DNA damage. Carcinogen-treated HIPK1-/- mice developed fewer and smaller skin tumors than HIPK1+/+ mice. HIPK1 may thus play a role in tumorigenesis, perhaps by means of the regulation of p53 and/or Mdm2.

Item Type: Paper
Uncontrolled Keywords: P53 PROTEIN DNA-BINDING PHOSPHORYLATION TRANSACTIVATION ACTIVATION AMPLIFICATION INVOLVEMENT PROMOTES MUTATION GROWTH
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
organism description > yeast
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: Matt Covey
Date: April 2003
Date Deposited: 01 Jul 2013 15:38
Last Modified: 01 Jul 2013 15:38
PMCID: PMC154362
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27915

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