Covalent NEDD8 Conjugation Increases RCAN1 Protein Stability and Potentiates Its Inhibitory Action on Calcineurin

Eun Hye Noh, Hee Sook Hwang, Hee Sun Hwang, Boram Min, Eunju Im, Kwang Chul Chung

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Similar to ubiquitin, regulatory roles for NEDD8 (neural precursor cell-expressed developmentally down-regulated 8) are being clarified during cell growth, signal transduction, immune response, and development. However, NEDD8 targets and their functional alterations are not well known. Regulator of calcineurin 1 (RCAN1/DSCR1P1) is located near the Down syndrome critical region on the distal part of chromosome 21, and its gene product is an endogenous inhibitor of calcineurin signaling. RCAN1 is modified by ubiquitin and consequently undergoes proteasomal degradation. Here we report that NEDD8 is conjugated to RCAN1 (RCAN1-1S) via three lysine residues, K96, K104, and K107. Neddylation enhances RCAN1 protein stability without affecting its cellular location. In addition, we found that neddylation significantly inhibits proteasomal degradation of RCAN1, which may underlie the ability of NEDD8 to enhance RCAN1 stability. Furthermore, neddylation increases RCAN1 binding to calcineurin, which potentiates its inhibitory activity toward downstream NFAT signaling. The present study provides a new regulatory mechanism of RCAN1 function and highlights an important role for diverse RCAN1-involved cellular physiology.

Original languageEnglish
Article numbere48315
JournalPloS one
Volume7
Issue number10
DOIs
Publication statusPublished - 2012 Oct 31

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Covalent NEDD8 Conjugation Increases RCAN1 Protein Stability and Potentiates Its Inhibitory Action on Calcineurin'. Together they form a unique fingerprint.

  • Cite this