BRCA1 and c-Myc Associate to Transcriptionally Repress Psoriasin, a DNA Damage-Inducible Gene


Autoria(s): Kennedy, Richard D.; Gorski, Julia J.; Quinn, Jennifer E.; Stewart, Gail E.; James, Colin R.; Moore, Stephen; Mulligan, Karl; Emberley, Ethan D.; Lioe, Tong F.; Morrison, Patrick J.; Mullan, Paul B.; Reid, George; Johnston, Patrick G.; Watson, Peter H.; Harkin, D. Paul
Data(s)

15/11/2005

Resumo

Evidence is accumulating to suggest that some of the diverse functions associated with BRCA1 may relate to its ability to transcriptionally regulate key downstream target genes. Here, we identify S100A7 (psoriasin), S100A8, and S100A9, members of the S100A family of calcium-binding proteins, as novel BRCA1-repressed targets. We show that functional BRCA1 is required for repression of these family members and that a BRCA1 disease–associated mutation abrogates BRCA1-mediated repression of psoriasin. Furthermore, we show that BRCA1 and c-Myc form a complex on the psoriasin promoter and that BRCA1-mediated repression of psoriasin is dependent on functional c-Myc. Finally, we show that psoriasin expression is induced by the topoisomerase IIA poison, etoposide, in the absence of functional BRCA1 and increased psoriasin expression enhances cellular sensitivity to this chemotherapeutic agent. Therefore, we identified a novel transcriptional mechanism that is likely to contribute to BRCA1-mediated resistance to etoposide.

Identificador

https://pure.qub.ac.uk/portal/en/publications/brca1-and-cmyc-associate-to-transcriptionally-repress-psoriasin-a-dna-damageinducible-gene(7cb72895-9fff-4667-93bc-ba1e5098b5c2).html

https://doi.org/10.1158/0008-5472.CAN-05-1841

http://www.scopus.com/inward/record.url?scp=28544447228&partnerID=8YFLogxK

Idioma(s)

eng

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Kennedy , R D , Gorski , J J , Quinn , J E , Stewart , G E , James , C R , Moore , S , Mulligan , K , Emberley , E D , Lioe , T F , Morrison , P J , Mullan , P B , Reid , G , Johnston , P G , Watson , P H & Harkin , D P 2005 , ' BRCA1 and c-Myc Associate to Transcriptionally Repress Psoriasin, a DNA Damage-Inducible Gene ' , Cancer Research , vol. 65 , no. 22 , pp. 10265-10272 . https://doi.org/10.1158/0008-5472.CAN-05-1841

Palavras-Chave #/dk/atira/pure/subjectarea/asjc/1300/1306 #Cancer Research #/dk/atira/pure/subjectarea/asjc/2700/2730 #Oncology
Tipo

article