Novel Interaction Between Nuclear Coactivator CBP and the Protein Inhibitor of Activated Stat1 (PIAS1)

Abstract

cAMP response element binding protein (CREB)-binding protein (CBP) is a multifunctional transcriptional coactivator that plays important roles in gene regulation. CBP is expressed in murine embryonic orofacial tissue, where it is developmentally regulated. To identify nuclear factors associated with CBP in developing orofacial tissue, a yeast two-hybrid screen of a cDNA library derived from embryonic orofacial tissue from gestational days 11-13 mouse embryos was conducted. Using the carboxy terminal region of CBP as bait, the protein inhibitor of activated Stat1 (PIAS1) was identified as a novel CBP binding protein. The association of PIAS1 with CBP was confirmed in vitro by glutathione S-transferase (GST) pull-down assays and in vivo by coimmunoprecipitation. Reporter assays demonstrated that PIAS1 inhibited CBP-mediated transcriptional activation in the presence or absence of transforming growth factor-beta (TGF-beta). These results identify PIAS1 as a novel binding partner for CBP and inhibitor of CBP-mediated transcription, suggesting that PIAS1 might play a role in regulating cell proliferation, migration, and differentiation during embryonic development.

Linking functions: an additional role for an intrinsically disordered linker domain in the transcriptional coactivator CBP

“…We expected that besides general, housekeeping proteins, shared partners in the two different libraries may point to functionally important and potentially disease-associated interaction partners of CBP/p300 mediated by ID3, mitigating the effect of known high false positive hit rates of Y2H. A total of 37 proteins were classified as potential ID3 binders, including 4 candidates that have already been described to interact with CBP or p300 (HIPK1 32 , PIAS1 33 , PAIS3 34 and TDG 35 ) (Fig. 2a).…”

NMDA receptor signaling mediates the expression of protein inhibitor of activated STAT1 (PIAS1) in rat hippocampus

“…It is also supported by the findings that PIAS1 promotes the sumoylation of metabotropic glutamate receptor 8 (Tang et al, 2005), whereas metabotropic glutamate receptors are involved in regulating synaptic activity (Luscher and Huber, 2010). Furthermore, PIAS1 was found to interact with the CREB-binding protein (CBP) (Yin et al, 2005), whereas CBP is a transcriptional coactivator for CREB and the CREB/CBP complex is suggested to mediate the memory-enhancing effect of histone deacetylase (HDAC) inhibitors through regulation of target gene expression (Vecsey et al, 2007). Moreover, our results revealed that PIAS1 expression is also regulated by PI-3 kinase signaling through the mediation of CREB because both LY294002 and wortmannin treatments down-regulated the expression of PIAS1 accompanied by a decreased phosphorylation level of CREB.…”

Modulation of type I interferon induction by porcine reproductive and respiratory syndrome virus and degradation of CREB-binding protein by non-structural protein 1 in MARC-145 and HeLa cells

“…CBP possesses histone acetyltransferase activity and dissociates histones for chromatin relaxation in the promoter region. The CBP/p300 co-activators function in concert with a variety of transcription factors including c-Myb, p53, STATs, NF-κB, PIAS1, and the IRF family (Barlev et al, 2001;Lin et al, 2000;Ma et al, 2005;Oelgeschläger et al, 1996;Yin et al, 2005;Zhong et al, 2002). Therefore, CBP acts as an important regulator for many cellular processes.…”