tailieunhanh - Báo cáo khoa học: CREB)a real culprit in oncogenesis

The cAMP response element-binding protein (CREB) is a stimulus-induced transcription factor that responds rapidly to phosphorylation and⁄or coac-tivator activation. Regulated activation of CREB has a significant impact on cellular growth, proliferation and survival. | ễFEBS Journal MINIREVIEW CREB - a real culprit in oncogenesis Yeung-Tung Siu and Dong-Yan Jin Department of Biochemistry The University of Hong Kong Hong Kong China Keywords CREB fusion oncoprotein human T-cell leukemia virus type I oncoprotein Tax oncogenesis proto-oncogene TORC coactivators Correspondence . Jin Department of Biochemistry The University of Hong Kong Third Floor Laboratory Block Faculty of Medicine Building 21 Sassoon Road Hong Kong Fax 852 2855 1254 Tel 852 2819 9491 E-mail dyjin@ The cAMP response element-binding protein CREB is a stimulus-induced transcription factor that responds rapidly to phosphorylation and or coactivator activation. Regulated activation of CREB has a significant impact on cellular growth proliferation and survival. To overturn the cellular control of these processes tumor cells have developed various mechanisms to achieve constitutive activation of CREB including gene amplification chromosome translocation interaction with viral oncoproteins and inactivation of tumor suppressor genes. These mechanisms converge on the phosphorylation of CREB and or the activation of transducer of regulated CREB activity TORC coactivators to effect uncontrolled proliferation of cells. This minireview summarizes the different lines of existing evidence that support a direct role of CREB in oncogenesis. Received 14 February 2007 accepted 27 April 2007 doi Introduction The cAMP response element-binding protein CREB is a well characterized transcription factor of the basic leucine zipper bZIP family 1 . In response to various stimuli such as growth factors neurotransmitters stress signals and other agents that elevate intracellular cAMP or Ca2 levels CREB is activated through phosphorylation at Ser133 and or nuclear translocation of transducer of regulated CREB activity TORC coactivators 1-4 . The activation of CREB turns on the transcription of more than 5000 target genes including proto-oncogenes