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Cell Cycle. 2018;17(18):2243-2255. doi: 10.1080/15384101.2018.1522912. Epub 2018 Sep 25.

PTPN14 regulates Roquin2 stability by tyrosine dephosphorylation.

Author information

1
a Department of Cancer Biology, Perelman School of Medicine , University of Pennsylvania , Philadelphia , PA , USA.
2
b The Stowers Institute of Medical Research , Kansas , MO , USA.
3
c Department of Pathology and Laboratory Medicine , The University of Kansas Medical Center , Kansas , KS , USA.

Abstract

Protein phosphorylation regulates a variety of cellular signaling pathways and fundamental mechanisms in cells. In this paper, we demonstrate that the mRNA decay factor Roquin2 is phosphorylated at tyrosine residue in position 691 in vivo. This phosphorylation disrupts the interaction with KLHL6, the E3 ligase for Roquin2. Furthermore, we establish that the tyrosine phosphatase PTPN14 specifically interacts with Roquin2 through its phosphatase domain and dephosphorylates Roquin2 tyrosine 691. Overexpression of PTPN14 promotes Roquin2 degradation in a KLHL6-dependant manner by promoting interaction with KLHL6. Collectively, our findings reveal that PTPN14 negatively regulates the protein stability of Roquin2, thereby adding a new layer of regulation to the KLHL6-Roquin2 axis.

KEYWORDS:

Cullin E3 ligase; Protein degradation; phosphorylation; post-translational modification; ubiquitin proteasome system

PMID:
30209976
PMCID:
PMC6226225
[Available on 2019-09-25]
DOI:
10.1080/15384101.2018.1522912

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