BRD7, a novel bromodomain gene, inhibits G1-S progression by transcriptionally regulating some important molecules involved in ras/MEK/ERK and Rb/E2F pathways.
Bromodomain is a 110 amino acid domain. It is evolutionally conserved and is found in proteins strongly implicated in signal-dependent transcriptional regulation. BRD7 is a novel bromodomain gene and it is downexpressed in nasopharyngeal carcinoma (NPC) biopsies and cell lines; its function is poorly understood. In the present study, tet-on inducible expression system was used to investigate the role of BRD7 in cell growth and cell cycle progression. We found that ectopic expression of BRD7 in NPC cells inhibited cell growth and cell cycle progression from G1 to S. We further performed cell cycle cDNA array to screen potential transcriptional targets of BRD7 in cell cycle. Thirteen important signaling molecules, mainly implicated in ras/MEK/ERK and Rb/E2F pathways, were differentially expressed by induction of BRD7. Moreover, we observed that BRD7 could regulate the promoter activity of E2F3, one of its targets. Taken together, the present study indicated that BRD7 inhibited G1-S progression by transcriptionally regulating some important molecules involved in ras/MEK/ERK and Rb/E2F pathways and suggested that BRD7 may present a promising candidate of NPC trade mark associated tumor suppressor gene.
Zhou
Jie
J
Cancer Research Institute, Xiang-Ya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.
Ma
Jian
J
Zhang
Bi-Cheng
BC
Li
Xiao-Ling
XL
Shen
Shou-Rong
SR
Zhu
Shi-Guo
SG
Xiong
Wei
W
Liu
Hua-Ying
HY
Huang
He
H
Zhou
Ming
M
Li
Gui-Yuan
GY
D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D003114:Colony-Forming Units Assay; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050684:E2F Transcription Factors; D050699:E2F3 Transcription Factor; D005434:Flow Cytometry; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D011905:Genes, ras; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050699:E2F3 Transcription Factor; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D018631:ras Proteins; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins