tailieunhanh - Báo cáo khoa học: TORC-SIK cascade regulates CREB activity through the basic leucine zipper domain

The transcription factor cAMP response element-binding protein (CREB) plays important roles in gene expression induced by cAMP signaling and is believed to be activated when its Ser133 is phosphorylated. However, the discovery of Ser133-independent activation by the activation of transducer of regulated CREB activity coactivators (TORC) and repression by salt inducible kinase cascades suggests that Ser133-independent regulation of CREB is also important. | ễFEBS Journal MINIREVIEW TORC-SIK cascade regulates CREB activity through the basic leucine zipper domain Hiroshi Takemori1 Junko Kajimura1 and Mitsuhiro Okamoto2 1 Laboratory of Cell Signaling and Metabolism National institute of BiomedicalInnovation Osaka Japan 2 Faculty of Contemporary Human Life Science Tezukayama University Nara Japan Keywords bZIP Ca2 cAMP coactivator CRE CREB salt SIK TORC transcription Correspondence H. Takemori Laboratory of CellSignaling and Metabolism National institute of Biomedical innovation 7-6-8 Asagi Saito Ibaraki Osaka 567-0085 Japan Fax 81 72 641 9836 Tel 81 72 641 9834 E-mail takemori@ The transcription factor cAMP response element-binding protein CREB plays important roles in gene expression induced by cAMP signaling and is believed to be activated when its Ser133 is phosphorylated. However the discovery of Ser133-independent activation by the activation of transducer of regulated CREB activity coactivators TORC and repression by salt inducible kinase cascades suggests that Ser133-independent regulation of CREB is also important. The activation and repression are mediated by the basic leucine zipper domain of CREB. In this review we focus on the basic leucine zipper domain in the regulation of transcriptional activity of CREB and describe the functions of TORC and salt inducible kinase. Received 29 January 2007 revised 1 May 2007 accepted 7 May 2007 doi Introduction The cAMP response element-binding protein CREB is a basic leucine zipper bZIP transcription factor which shares properties with other CREB members the CRE-modulator CREM and activating transcription factor 1 ATF1 . CREB members are approximately 70 homologous overall and are more than 90 homologous within their bZIPs and core sequences in the transactivation domain known as the kinase inducible domain KID . Serine residue 133 Ser133 in the KID of CREB and the equivalent residues of CREM ATF1 are phosphorylated by a variety