title: XLGαolf regulates expression of p27Kip1 in a CSN5 and CDK2 dependent manner.
abstract: XLGα(olf) is an extra large transcriptional variant of the heterotrimeric G protein, Gα(olf), which we previously reported to be localized in the Golgi apparatus and interacted with Rab3A and Rab8A through its N-terminal region. However, many physiological functions of XLGα(olf) remain to be elucidated. In this study, performance of yeast two-hybrid screening with XLGα(olf) allowed isolation of COP9 signalosome subunit 5 (CSN5), known to regulate the p27(Kip1) protein level through a proteasome dependent pathway. Co-immunoprecipitation experiments followed by Western blotting also showed association of CSN5 with XLGα(olf) linked to down-regulation of p27(Kip1). Gene silencing of endogenous CSN5 by siRNA attenuated the XLGα(olf)-mediated down-regulation, which was also demonstrated to require CDK2. Both knock down of CDK2 and the treatment with a CDK2 inhibitor reversed the reduction of p27(Kip1) due to XLGα(olf). Our findings provide important clues to understanding physiological functions of XLGα(olf).
authors: Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Konohana-ku, Osaka 554-8558, Japan. akitak@sc.sumitomo-chem.co.jp
authors: Kazumasa
authors: K
authors: Akita
authors: Yasuhiko
authors: Y
authors: Takahashi
authors: Naoko
authors: N
authors: Takata
authors: Michiru
authors: M
authors: Hashimoto
authors: Masaki
authors: M
authors: Kataoka
authors: Yoshitaka
authors: Y
authors: Tomigahara
authors: Koichi
authors: K
authors: Saito
mesh_terms: D000075686:COP9 Signalosome Complex; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D020798:Two-Hybrid System Techniques
chemical_list: D044385:GTP-Binding Protein alpha Subunits; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C084618:olfactory G protein subunit alpha olf; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051357:Cyclin-Dependent Kinase 2; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex