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 language | English |
|---|---|
| Pages (from-to) | 2448-2459 |
| Number of pages | 12 |
| Journal | Journal of Cell Science |
| Volume | 127 |
| Issue number | 11 |
| DOIs | |
| State | Published - Jan 1 2014 |
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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 journal › Article
}
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 -