A novel function of Nur77: physical and functional association with protein kinase C.
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.
Kim
Hyungsoo
H
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.
Kim
Bu-Yeon
BY
Soh
Jae-Won
JW
Cho
Eun-Jung
EJ
Liu
Jun O
JO
Youn
Hong-Duk
HD
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
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