Dataset Information


Gene regulation by phosphomimetic Myc and retinoic acid

ABSTRACT: We aimed to investigate the E-box and Max-independent functions of the oncogene Myc in gene regulation and differentiation of leukemic cells. Expression in HL60 leukemic cells of a mutant form of Myc with impaired Max and E-box interaction by replacing the phosphorylation sites of Pak2 kinase to aspartic acid (MycD), resulted in downregulation of 235 genes and, interestingly, upregulation of 586 genes. Eleven percent of the genes upregulated by MycD coincided with those stimulated by a short treatment of retinoic acid (RA) alone. When leukemic cells expressing MycD were stimulated with RA, the overlap with the RA-alone signature increased to 32% (492/1556 genes). Importantly, 320 of these 492 bona-fide direct RA target genes were specifically superactivated in presence of MycD (MycD+RA>RA), and not by MycA (MycD+RA>MycA+RA), further suggesting a synergy between the two pathways. The list of superactivated genes included important regulators of development and differentiation such as GATA6, ICAM1 and HOX genes, whose expression was validated in independent experiments by RT-qPCR. Induced gene expression in HL60 cells was measured after a short-treatment of retinoic acid (100nM, 4 hours). Cells were either wild-type or expressing ER-tagged MycD or MycA. Four biologically independent experiments were performed at each time.

ORGANISM(S): Homo sapiens  

SUBMITTER: Guglielmo Roma   Luciano Di Croce  Iris Uribesalgo 

PROVIDER: E-GEOD-24731 | ArrayExpress | 2012-01-05



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MYC proto-oncogene is a key player in cell homeostasis that is commonly deregulated in human carcinogenesis(1). MYC can either activate or repress target genes by forming a complex with MAX (ref. 2). MYC also exerts MAX-independent functions that are not yet fully characterized(3). Cells possess an intrinsic pathway that can abrogate MYC-MAX dimerization and E-box interaction, by inducing phosphorylation of MYC in a PAK2-dependent manner at three residues located in its helix-loop-helix domain(4  ...[more]

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