A novel function of Nur77: physical and functional association with protein kinase C

Hyungsoo Kim; Bu-Yeon Kim; Jae-Won Soh; Eun-Jung Cho; Jun O Liu; Hong-Duk Youn

doi:10.1016/j.bbrc.2006.07.167

A novel function of Nur77: physical and functional association with protein kinase C

Biochem Biophys Res Commun. 2006 Sep 29;348(3):950-6. doi: 10.1016/j.bbrc.2006.07.167. Epub 2006 Aug 4.

Authors

Hyungsoo Kim¹, Bu-Yeon Kim, Jae-Won Soh, Eun-Jung Cho, Jun O Liu, Hong-Duk Youn

Affiliation

¹ 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.

PMID: 16904076
DOI: 10.1016/j.bbrc.2006.07.167

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Catalytic Domain / physiology
Cell Line
DNA-Binding Proteins / chemistry*
DNA-Binding Proteins / metabolism
DNA-Binding Proteins / physiology*
Humans
Jurkat Cells
Mice
Mice, Transgenic
Nuclear Receptor Subfamily 4, Group A, Member 1
Protein Kinase C / antagonists & inhibitors
Protein Kinase C / metabolism*
Protein Kinase C / physiology
Receptors, Cytoplasmic and Nuclear / chemistry*
Receptors, Cytoplasmic and Nuclear / metabolism
Receptors, Cytoplasmic and Nuclear / physiology*
Receptors, Steroid / chemistry*
Receptors, Steroid / metabolism
Receptors, Steroid / physiology*
Transcription Factors / chemistry*
Transcription Factors / metabolism
Transcription Factors / physiology*
Two-Hybrid System Techniques

Substances

DNA-Binding Proteins
NR4A1 protein, human
Nr4a1 protein, mouse
Nuclear Receptor Subfamily 4, Group A, Member 1
Receptors, Cytoplasmic and Nuclear
Receptors, Steroid
Transcription Factors
Protein Kinase C