Document Detail

Frequent phosphorylation at serine 392 in overexpressed p53 protein due to missense mutation in carcinoma of the urinary tract.
MedLine Citation:
PMID:  12081208     Owner:  NLM     Status:  MEDLINE    
Post-transcriptional modification of p53 by phosphorylation has been proposed to be an important mechanism of p53 stabilization and functional regulation. Phosphorylation of p53 Ser392, in particular, activates specific DNA binding functions by stabilizing p53 tetramer formation. This study evaluated the relationship between p53 Ser392 phosphorylation and various types of p53 missense mutation detected in urothelial transitional cell carcinomas (TCCs), with stratification of the mutations according to the functional domains elucidated by the crystal structure of the p53 protein. Of 41 TCCs with missense mutations, 26 (63.4%) exhibited immunopositivity with Ser392 phospho-specific p53 antibody. In comparison to structural mutations, the missense mutations at exon 7 (p=0.0307) or located in regions that affect direct DNA binding ability (p = 0.0273) were significantly associated with Ser392 immunopositivity. No statistically significant relationship was found between Ser392 immunoreactivity and other different types of p53 mutation. The prevalence of cases exhibiting Ser392-positive immunostaining was higher for high-grade (p <0.0001) and advanced-stage TCCs (p =0.0119) than for TCCs with wild-type p53. No significant relationship was found between Ser392 immunoreactivity and apoptotic index in urothelial TCCs. These in vivo findings indicate that Ser392 phosphorylation frequently occurs in mutant form p53 in TCCs. Because mutant form p53 can act dominant-negatively by heterooligomerization with wild-type p53, these findings also suggest that Ser392 phosphorylation might activate tetramer formation to promote the dominant-negative effects of mutant form p53, and thereby contribute to proliferation of aggressive TCCs.
Mutsuo Furihata; Atsushi Kurabayashl; Manabu Matsumoto; Hiroshi Sonobe; Yuji Ohtsuki; Naotami Terao; Morimasa Kuwahara; Taro Shuin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pathology     Volume:  197     ISSN:  0022-3417     ISO Abbreviation:  J. Pathol.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-06-25     Completed Date:  2002-07-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  82-8     Citation Subset:  IM    
Department of Pathology II, Kochi Medical School, Nankoku, Japan.
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MeSH Terms
Aged, 80 and over
Carcinoma, Transitional Cell / genetics*,  metabolism,  pathology
Genes, p53
Middle Aged
Mutation, Missense*
Serine / genetics*
Tumor Suppressor Protein p53 / metabolism*
Urologic Neoplasms / genetics*,  metabolism,  pathology
Reg. No./Substance:
0/Tumor Suppressor Protein p53; 56-45-1/Serine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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