ATAD2 is a novel cofactor for MYC, overexpressed and amplified in aggressive tumors

TY - JOUR

T1 - ATAD2 is a novel cofactor for MYC, overexpressed and amplified in aggressive tumors

AU - Ciró, Marco

AU - Prosperini, Elena

AU - Quarto, Micaela

AU - Grazini, Ursula

AU - Walfridsson, Julian

AU - McBlane, Fraser

AU - Nucifero, Paolo

AU - Pacchiana, Giovanni

AU - Capra, Maria

AU - Christensen, Jesper

AU - Helin, Kristian

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1158/0008-5472.CAN-09-2131

DO - 10.1158/0008-5472.CAN-09-2131

M3 - Journal article

C2 - 19843847

SN - 0008-5472

VL - 69

SP - 8491

EP - 8498

JO - Cancer Research

JF - Cancer Research

IS - 21

ER -