Differential gene regulation by the SRC family of coactivators.
SRCs (steroid receptor coactivators) are required for nuclear receptor-mediated transcription and are also implicated in the transcription initiation by other transcription factors, such as STATs and NFkappaB. Despite phenotypic manifestations in gene knockout mice for SRC-1, GRIP1, and AIB1 of the SRC (Steroid Receptor Coactivator) family indicating their differential roles in animal physiology, there is no clear evidence, at the molecular level, to support a functional specificity for these proteins. We demonstrated in this report that two species of SRC coactivators, either as AIB1:GRIP1 or as AIB1:SRC-1 are recruited, possibly through heterodimerization, on the promoter of genes that contain a classical hormone responsive element (HRE). In contrast, on non-HRE-containing gene promoters, on which steroid receptors bind indirectly, either GRIP1 or SRC-1 is recruited as a monomer, depending on the cellular abundance of the protein. Typically, non-HRE-containing genes are early genes activated by steroid receptors, whereas HRE-containing genes are activated later. Our results also showed that SRC proteins contribute to the temporal regulation of gene transcription. In addition, our experiments revealed a positive correlation between AIB1/c-myc overexpression in ER+ breast carcinoma samples, suggesting a possible mechanism for AIB1 in breast cancer carcinogenesis.
Zhang
Hua
H
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100083, China.
Yi
Xia
X
Sun
Xiaojing
X
Yin
Na
N
Shi
Bin
B
Wu
Huijian
H
Wang
Dan
D
Wu
Ge
G
Shang
Yongfeng
Y
D000951:Antigens, Neoplasm / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D017931:DNA Primers; C120762:EBAG9 protein, human; C491310:GRIP1 protein, human; C489427:MYC protein, human; D009419:Nerve Tissue Proteins; D016271:Proto-Oncogene Proteins c-myc; D018091:Receptors, AMPA; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3