The role of retinoblastoma-associated proteins 46 and 48 in estrogen receptor alpha mediated gene expression.
The differential recruitment of coregulatory proteins to the DNA-bound estrogen receptor alpha (ERalpha) plays a critical role in mediating estrogen-responsive gene expression. We previously isolated and identified retinoblastoma-associated proteins 46 (RbAp46) and 48 (RbAp48), which are associated with chromatin remodeling, histone deacetylation, and transcription repression, as proteins associated with the DNA-bound ERalpha. We now demonstrate that RbAp46 and RbAp48 interact with ERalphain vitro and in vivo, associate with ERalpha at endogenous, estrogen-responsive genes, and alter expression of endogenous, ERalpha-activated and -repressed genes in MCF-7 breast cancer cells. Our findings reveal that RbAp48 limits expression of estrogen-responsive genes and that RbAp46 modulates estrogen responsiveness in a gene-specific manner. The ability of RbAp46 and RbAp48 to interact with ERalpha and influence its activity reveals yet another role for these multifunctional proteins in regulating gene expression.
Creekmore
Amy L
AL
Department of Cell and Developmental Biology, University of Illinois, Urbana, IL 61801, United States.
Walt
Kjirsten A
KA
Schultz-Norton
Jennifer R
JR
Ziegler
Yvonne S
YS
McLeod
Ian X
IX
Yates
John R
JR
Nardulli
Ann M
AM
D001943:Breast Neoplasms / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056505:Retinoblastoma-Binding Protein 4; D056524:Retinoblastoma-Binding Protein 7; D014158:Transcription, Genetic
D002352:Carrier Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D009687:Nuclear Proteins; C082637:RBBP4 protein, human; C490746:RBBP7 protein, human; D056505:Retinoblastoma-Binding Protein 4; D056524:Retinoblastoma-Binding Protein 7