title: A novel function of Nur77: physical and functional association with protein kinase C.
abstract: Despite the involvement in diverse physiological process and pleiotropic expression profile, the molecular functions of Nur77 are not likely to be fully elucidated. From the effort to find a novel function of Nur77, we detected molecular interaction between Nur77 and PKC. Details of interaction revealed that C-terminal ligand binding domain (LBD) of Nur77 specifically interacted with highly conserved glycine-rich loop of PKC required for catalytic activity. This molecular interaction resulted in inhibition of catalytic activity of PKCtheta by Nur77. C-terminal LBD of Nur77 is sufficient for inhibiting the phosphorylation of substrate by PKCtheta. Ultimately, inhibition of catalytic activity by Nur77 is deeply associated with repression of PKC-mediated activation of AP-1 and NF-kappaB. Therefore, these findings demonstrate a novel function of Nur77 as a PKC inhibitor and give insights into molecular mechanisms of various Nur77-mediated physiological phenomena.
authors.affiliation: Department of Biochemistry and Molecular Biology, Cancer Research Institute, Interdisciplinary Program in Genetic Engineering, Seoul National University College of Medicine, 28 Yongon-dong, Chongro-gu, Seoul 110-799, Republic of Korea.
authors.forename: Hyungsoo
authors.initials: H
authors.lastname: Kim
authors.forename: Bu-Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Soh
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Cho
authors.forename: Jun O
authors.initials: JO
authors.lastname: Liu
authors.forename: Hong-Duk
authors.initials: HD
authors.lastname: Youn
mesh_terms: D000818:Animals; D020134:Catalytic Domain / Q000502:physiology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008822:Mice, Transgenic; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D011987:Receptors, Steroid / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D020798:Two-Hybrid System Techniques
chemical_list: D004268:DNA-Binding Proteins; C539821:NR4A1 protein, human; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D011493:Protein Kinase C