Regulation of Cop9 signalosome activity by the EF-hand Ca2+-binding protein tescalcin

Konstantin Levay, Vladlen Z. Slepak

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The Ca2+-binding protein tescalcin is known to be involved in hematopoietic cell differentiation; however, this mechanism is poorly understood. Here, we identify CSN4 (subunit 4 of the COP9 signalosome) as a novel binding partner of tescalcin. The COP9 signalosome (CSN) is a multiprotein complex that is essential for development in all eukaryotes. This interaction is selective, Ca2+- dependent and involves the PCI domain of CSN4 subunit. We then investigated tescalcin and CSN activity in human erythroleukemia HEL and promyelocytic leukemia K562 cells and find that phorbol 12-myristate 13-acetate (PMA)-induced differentiation, resulting in the upregulation of tescalcin, coincides with reduced deneddylation of cullin-1 (Cul1) and stabilization of p27Kip1-molecular events that are associated with CSN activity. The knockdown of tescalcin led to an increase in Cul1 deneddylation, expression of F-box protein Skp2 and the transcription factor c-Jun, whereas the levels of cell cycle regulators p27Kip1 and p53 decreased. These effects are consistent with the hypothesis that tescalcin might play a role as a negative regulator of CSN activity towards Cul1 in the process of induced cell differentiation.

Original languageEnglish (US)
Pages (from-to)2448-2459
Number of pages12
JournalJournal of Cell Science
Volume127
Issue number11
DOIs
StatePublished - Jun 2014

Keywords

  • Cell cycle
  • COP9 signalosome
  • Cullin
  • P27
  • Tescalcin

ASJC Scopus subject areas

  • Cell Biology

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