Document Detail


Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human.
MedLine Citation:
PMID:  12881723     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Linkage analysis and haplotype mapping in interspecific mouse crosses (Mus musculus x Mus spretus) identified the gene encoding Aurora2 (Stk6 in mouse and STK15 in human) as a candidate skin tumor susceptibility gene. The Stk6 allele inherited from the susceptible M. musculus parent was overexpressed in normal cells and preferentially amplified in tumor cells from F(1) hybrid mice. We identified a common genetic variant in STK15 (resulting in the amino acid substitution F31I) that is preferentially amplified and associated with the degree of aneuploidy in human colon tumors. The Ile31 variant transforms rat1 cells more potently than the more common Phe31 variant. The E2 ubiquitin-conjugating enzyme UBE2N was a preferential binding partner of the 'weak' STK15 Phe31 variant form in yeast two-hybrid screens and in human cells. This interaction results in colocalization of UBE2N with STK15 at the centrosomes during mitosis. These results are consistent with an important role for the Ile31 variant of STK15 in human cancer susceptibility.
Authors:
Amanda Ewart-Toland; Paraskevi Briassouli; John P de Koning; Jian-Hua Mao; Jinwei Yuan; Florence Chan; Lucy MacCarthy-Morrogh; Bruce A J Ponder; Hiroki Nagase; John Burn; Sarah Ball; Maria Almeida; Spiros Linardopoulos; Allan Balmain
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nature genetics     Volume:  34     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-08-18     Completed Date:  2003-09-22     Revised Date:  2011-07-11    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  403-12     Citation Subset:  IM    
Affiliation:
UCSF Comprehensive Cancer Center, University of California, San Francisco, California 94115, USA.
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MeSH Terms
Descriptor/Qualifier:
Aneuploidy
Animals
Cell Division / genetics
Chromosome Mapping
Chromosomes, Human, Pair 20 / genetics
Crosses, Genetic
Gene Amplification
Genetic Variation
Haplotypes
Humans
Ligases / genetics,  metabolism
Mice
Mice, Inbred Strains
Muridae
Oncogenes*
Physical Chromosome Mapping
Protein-Serine-Threonine Kinases / genetics*,  metabolism
Recombinant Proteins / genetics,  metabolism
Skin Neoplasms / genetics
Two-Hybrid System Techniques
Ubiquitin-Conjugating Enzymes*
Chemical
Reg. No./Substance:
0/Recombinant Proteins; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/aurora kinase; EC 6.-/Ligases; EC 6.3.2.19/UBE2N protein, human; EC 6.3.2.19/Ubiquitin-Conjugating Enzymes
Comments/Corrections
Comment In:
Nat Genet. 2003 Aug;34(4):353-4   [PMID:  12923537 ]

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


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