title: cAMP signalling decreases p300 protein levels by promoting its ubiquitin/proteasome dependent degradation via Epac and p38 MAPK in lung cancer cells.
abstract: The transcriptional coactivator p300 functions as a histone acetyltransferase and a scaffold for transcription factors. We investigated the effect of cAMP signalling on p300 expression. The activation of cAMP signalling by the expression of constitutively active Gαs or by treatment with isoproterenol decreased the p300 protein expression in lung cancer cells. Isoproterenol promoted the ubiquitination and subsequent proteasomal degradation of p300 in an Epac-dependent manner. Epac promoted p300 degradation by inhibiting the activity of p38 MAPK. It is concluded that cAMP signalling decreases the level of the p300 protein by promoting its ubiquitin-proteasome dependent degradation, which is mediated by Epac and p38 MAPK, in lung cancer cells.
authors.affiliation: Department of Biochemistry and Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Min-Jae
authors.initials: MJ
authors.lastname: Jeong
authors.forename: Eui-Jun
authors.initials: EJ
authors.lastname: Kim
authors.forename: Eun-Ah
authors.initials: EA
authors.lastname: Cho
authors.forename: Sang-Kyu
authors.initials: SK
authors.lastname: Ye
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.forename: Yong-Sung
authors.initials: YS
authors.lastname: Juhnn
mesh_terms: D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism*; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C116122:RAPGEF3 protein, human; D025801:Ubiquitin; D000242:Cyclic AMP; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D048051:p38 Mitogen-Activated Protein Kinases; D046988:Proteasome Endopeptidase Complex