ATAD2 is a novel cofactor for MYC, overexpressed and amplified in aggressive tumors.
The E2F and MYC transcription factors are critical regulators of cell proliferation and contribute to the development of human cancers. Here, we report on the identification of a novel E2F target gene, ATAD2, the predicted protein product of which contains both a bromodomain and an ATPase domain. The pRB-E2F pathway regulates ATAD2 expression, which is limiting for the entry into the S phase of the cell cycle. We show that ATAD2 binds the MYC oncogene and stimulates its transcriptional activity. ATAD2 maps to chromosome 8q24, 4.3 Mb distal to MYC, in a region that is frequently found amplified in cancer. Consistent with this, we show that ATAD2 expression is high in several human tumors and that the expression levels correlate with clinical outcome of breast cancer patients. We suggest that ATAD2 links the E2F and MYC pathways and contributes to the development of aggressive cancer through the enhancement of MYC-dependent transcription.
Ciró
Marco
M
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Prosperini
Elena
E
Quarto
Micaela
M
Grazini
Ursula
U
Walfridsson
Julian
J
McBlane
Fraser
F
Nucifero
Paolo
P
Pacchiana
Giovanni
G
Capra
Maria
M
Christensen
Jesper
J
Helin
Kristian
K
D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000251:Adenosine Triphosphatases; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D050684:E2F Transcription Factors / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D006657:Histones; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein; C113829:transformation-transcription domain-associated protein; D008156:Luciferases; D000251:Adenosine Triphosphatases; C544857:ATAD2 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities