TAILIEUCHUNG - Báo cáo khoa học: cAMP response element-binding protein (CREB) is imported into mitochondria and promotes protein synthesis

The cAMP response element-binding protein (CREB) is a ubiquitous transcription factor in the higher eukaryotes that, once phosphorylated, promotes transcription of cAMP response element-regulated genes. We have studied the mitochondrial import of CREB and its effect on the expression of mtDNA-encoded proteins. | ỊFEBS Journal cAMP response element-binding protein CREB is imported into mitochondria and promotes protein synthesis Domenico De Rasmo1 Anna Signorile1 Emilio Roca1 and Sergio Papa1 2 1 Department of MedicalBiochemistry Biology and Physics DIBIFIM University of Bari Italy 2 Institute of Biomembranes and Bioenergetics IBBE Consiglio Nazionale delle Ricerche Bari Italy Keywords cAMP cascade complex I CREB mitochondrial protein synthesis PKA Correspondence S. Papa Department of Medical Biochemistry Biology and Physics University of Bari Policlinico G. Cesare 70124 Bari Italy Fax 39 080 5448538 Tel 39 080 5448540 E-mail papabchm@ Received 9 March 2009 revised 26 May 2009 accepted 4 June 2009 The cAMP response element-binding protein CREB is a ubiquitous transcription factor in the higher eukaryotes that once phosphorylated promotes transcription of cAMP response element-regulated genes. We have studied the mitochondrial import of CREB and its effect on the expression of mtDNA-encoded proteins. 35S Methionine-labelled CREB synthesized in vitro in the Rabbit Reticulocyte Lysate system using a construct of the human cDNA was imported into the matrix of isolated rat liver mitochondria by a membrane potential and TOM complex-dependent process. The imported CREB caused cAMP-dependent promotion of the synthesis of mitochondrially encoded subunits of oxidative phosphorylation enzyme complexes. Thus CREB moves from the cytosol to mitochondria in addition to the nucleus and when phosphorylated by cAMP-dependent protein kinase promotes the expression of mitochondrial genes. doi Introduction The cAMP response element-binding protein CREB is a ubiquitous transcription factor in the higher eukaryotes that recognizes the DNA consensus sequence TGACGTCA the cAMP response element CRE in gene promoters 1 2 . Phosphorylation of CREB by cAMP-dependent protein kinase protein kinase A PKA as well as by Ca2 -dependent and other protein

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