CREB (cyclic AMP response element-binding protein) is a stimulus-induced transcription factor that plays pivotal roles in cell survival and proliferation. CREB is expressed in various tissues, and has important gene-regulating roles in the nervous system. The transactivation function of CREB is primarily regulated through Ser-133 phosphorylation by cAMP-dependent protein kinase A (PKA) and related kinases. CREB is phosphorylated at other sites in response to calcium influx and DNA damage. The DNA-damage responsive nuclear kinase, HIPK2, can phosphorylate Ser-271 but not Ser-133 in CREB, and this phosphorylation activates CREB transactivation function. Mutation of Ser-271 to Glu-271 potentiates the CREB transactivation function. Thus, phosphorylation of Ser-271 may be the mode of activation for CREB-dependent transcription in response to genotoxic stress.
Lonze, B.E. & Ginty, D.D. (2002) Neuron 35:605.
Gonzalez, G.A. & Montminy, M.R. (1989) Cell. 59(4):675.
*For more information, see UniProt Accession P16220
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*All molecular weights (MW) are confirmed by comparison to Bio-Rad Rainbow Markers and to western blot mobilities of known proteins with similar MW.
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