rasd1 modulates the coactivator function of nono in the cyclic amp pathwayrasd1调节环腺苷酸通路中的禁忌的共激活剂功能.pdfVIP

Rasd1 Modulates the Coactivator Function of NonO in the Cyclic AMP Pathway 1 1,2 1 1 Shufen Angeline Ong , Jen Jen Tan , Wai Loon Tew , Ken-Shiung Chen * 1 School of Biological Sciences, Department of Genomics and Genetics, Nanyang Technological University, Singapore, Singapore, 2 Agency for Science, Technology and Research, Singapore, Singapore Abstract All living organisms exhibit autonomous daily physiological and behavioural rhythms to help them synchronize with the environment. Entrainment of circadian rhythm is achieved via activation of cyclic AMP (cAMP) and mitogen-activated protein kinase signaling pathways. NonO (p54nrb) is a multifunctional protein involved in transcriptional activation of the cAMP pathway and is involved in circadian rhythm control. Rasd1 is a monomeric G protein implicated to play a pivotal role in potentiating both photic and nonphotic responses of the circadian rhythm. In this study, we have identified and validated NonO as an interacting partner of Rasd1 via affinity pulldown, co-immunoprecipitation and indirect immunofluorescence studies. The GTP-hydrolysis activity of Rasd1 is required for the functional interaction. Functional interaction of Rasd1-NonO in the cAMP pathway was investigated via reporter gene assays, chromatin immunoprecipitation and gene knockdown. We showed that Rasd1 and NonO interact at the CRE-site of specific target genes. These findings reveal a novel mechanism by which the coregulator activity of NonO can be modulated. Citation: Ong SA, Tan JJ, Tew WL, Chen K-S (2011) Rasd1 Modulates the Coactivator Function of NonO in the Cyclic AMP Pathway. PLoS ONE 6(9): e24401. doi:10.1371/journal.pone.0024401 Editor: Janet F. Partridge, St. Jude Children’s Research Hospital, United Stat