Linked Life Data

11916966

Source:http://linkedlifedata.com/resource/pubmed/id/11916966

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2002-6-3
pubmed:abstractText
Germ-line mutations in BRCA1 predispose individuals to breast and ovarian cancers. We observed a novel endogenous association of BRCA1 with Nmi (N-Myc-interacting protein) in breast cancer cells. Nmi was found to interact specifically with BRCA1, both in vitro and in vivo, by binding to two major domains in BRCA1, amino acid residues 298-683 and 1301-1863. Homodimerization of Nmi enhanced its association with BRCA1. Nmi functioned as an adaptor molecule to recruit c-Myc to a complex containing Nmi.c-Myc.BRCA1. Because c-Myc can activate transcription of the human telomerase reverse transcriptase gene (hTERT), we addressed the role of BRCA1 and Nmi in modulating c-Myc-induced hTERT promoter activity. Although Nmi or BRCA1 alone had no effect on c-Myc induced hTERT promoter activity, BRCA1 together with Nmi significantly inhibited this c-Myc induced hTERT promoter activity ( approximately 75% inhibition). Two mutated forms of BRCA1, a missense (A1708E) and a nonsense (Y1853X) that have been identified in familial breast cancers, associated with Nmi and c-Myc but failed to suppress c-Myc-induced hTERT promoter activity. These results demonstrate a novel pathogenic mechanism whereby mutations in BRCA1, via a novel transcription factor complex containing BRCA1, c-Myc, and Nmi, impair inhibition of c-Myc-induced hTERT promoter activity, which allows sustained activation of telomerase, a key enzyme in carcinogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20965-73
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer.
pubmed:affiliation
Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't