A novel C53/LZAP-interacting protein regulates stability of C53/LZAP and DDRGK domain-containing protein 1 (DDRGK1) and modulates NF-κB signaling

Jianchun Wu, Guohua Lei, Mei Mei, Yi Tang, Honglin Li

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

C53/LZAP (also named as Cdk5rap3) is a putative tumor suppressor that plays important roles in multiple cell signaling pathways, including DNA damage response and NF-κB signaling. Yet how its function is regulated remains largely unclear. Here we report the isolation and characterization of two novel C53/LZAP-interacting proteins, RCAD (Regulator of C53/LZAP and DDRGK1) and DDRGK1 (DDRGK domain-containing protein 1). Our co-immunoprecipitation assays confirmed their interactions, while gel filtration assay indicated that C53/LZAP and RCAD may form a large protein complex. Intriguingly, we found that RCAD knockdown led to dramatic reduction of C53/LZAP and DDRGK1 proteins. We also found that C53/LZAP and DDRGK1 became more susceptible to the proteasome-mediated degradation in RCAD knockdown cells, whereas their ubiquitination was significantly attenuated by RCAD overexpression. In addition, we found that RCAD, like C53/LZAP, also plays an important role in regulation of NF-κB signaling and cell invasion. Taken together, our findings strongly suggest that RCAD is a novel regulator of C53/LZAP tumor suppressor and NF-κB signaling.

Original languageEnglish (US)
Pages (from-to)15126-15136
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number20
DOIs
StatePublished - May 14 2010

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Protein Stability
Tumors
Assays
Proteins
Ubiquitination
Proteasome Endopeptidase Complex
Cell signaling
Immunoprecipitation
DNA Damage
Gel Chromatography
Neoplasms
Gels
Degradation
Protein Domains
DNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A novel C53/LZAP-interacting protein regulates stability of C53/LZAP and DDRGK domain-containing protein 1 (DDRGK1) and modulates NF-κB signaling. / Wu, Jianchun; Lei, Guohua; Mei, Mei; Tang, Yi; Li, Honglin.

In: Journal of Biological Chemistry, Vol. 285, No. 20, 14.05.2010, p. 15126-15136.

Research output: Contribution to journalArticle

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