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

Konstantin Levay, Vladlen Z Slepak

Research output: Contribution to journalArticle

7 Citations (Scopus)

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
Pages (from-to)2448-2459
Number of pages12
JournalJournal of Cell Science
Volume127
Issue number11
DOIs
StatePublished - Jan 1 2014

Fingerprint

EF Hand Motifs
Carrier Proteins
Cell Differentiation
F-Box Proteins
Multiprotein Complexes
Leukemia, Erythroblastic, Acute
K562 Cells
Eukaryota
Human Activities
Cell Cycle
Leukemia
Acetates
Transcription Factors
Up-Regulation
COP9 signalosome complex
Cullin 1

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Regulation of Cop9 signalosome activity by the EF-hand Ca2+-binding protein tescalcin. / Levay, Konstantin; Slepak, Vladlen Z.

In: Journal of Cell Science, Vol. 127, No. 11, 01.01.2014, p. 2448-2459.

Research output: Contribution to journalArticle

@article{852dc8f1739244e7bd89161cb8136f6b,
title = "Regulation of Cop9 signalosome activity by the EF-hand Ca2+-binding protein tescalcin",
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.",
keywords = "Cell cycle, COP9 signalosome, Cullin, P27, Tescalcin",
author = "Konstantin Levay and Slepak, {Vladlen Z}",
year = "2014",
month = "1",
day = "1",
doi = "10.1242/jcs.139592",
language = "English",
volume = "127",
pages = "2448--2459",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "11",

}

TY - JOUR

T1 - Regulation of Cop9 signalosome activity by the EF-hand Ca2+-binding protein tescalcin

AU - Levay, Konstantin

AU - Slepak, Vladlen Z

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - Cell cycle

KW - COP9 signalosome

KW - Cullin

KW - P27

KW - Tescalcin

UR - http://www.scopus.com/inward/record.url?scp=84901811021&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901811021&partnerID=8YFLogxK

U2 - 10.1242/jcs.139592

DO - 10.1242/jcs.139592

M3 - Article

VL - 127

SP - 2448

EP - 2459

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 11

ER -