NFATc1 phosphorylation by DYRK1A increases its protein stability

Heng Liu; Ketao Wang; Shuai Chen; Qian Sun; Yuankai Zhang; Long Chen; Xiulian Sun

doi:10.1371/journal.pone.0172985

NFATc1 phosphorylation by DYRK1A increases its protein stability

PLoS One. 2017 Feb 24;12(2):e0172985. doi: 10.1371/journal.pone.0172985. eCollection 2017.

Authors

Heng Liu^{1

2}, Ketao Wang¹, Shuai Chen², Qian Sun^{1

2}, Yuankai Zhang¹, Long Chen², Xiulian Sun^{1

3}

Affiliations

¹ Shenzhen Research Institute of Shandong University, Shenzhen, Guangdong Province, China.
² Otolaryngology Key Lab of Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.
³ Brain Research Institute, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.

Abstract

NFATs are transcription factors involved in immune activation and tumor progression. Previous reports showed that DYRK1A suppressed NFATc2 transcriptional activity through phosphorylation. Nonetheless, our results showed that DYRK1A increased NFATc1/αA protein level and subsequent transcriptional activity. DYRK1A phosphorylation of NFATc1/αA at S261, S278, S403 and S409 interfered with NFATc1 ubiquitination and ubiquitin-proteasome degradation. Our results imply that DYRK1A is a positive kinase in regulation of NFATc1.

MeSH terms

Amino Acid Motifs
Dyrk Kinases
HEK293 Cells
Humans
NFATC Transcription Factors / metabolism*
Phosphorylation
Proteasome Endopeptidase Complex / metabolism
Protein Serine-Threonine Kinases / metabolism*
Protein Stability
Protein-Tyrosine Kinases / metabolism*
Proteolysis
Ubiquitination*

Substances

NFATC Transcription Factors
NFATC1 protein, human
Protein-Tyrosine Kinases
Protein Serine-Threonine Kinases
Proteasome Endopeptidase Complex

Grants and funding

This work was supported by National Science Foundation of China (81101796, 81171030, 81322014), Shenzhen Science and Technology Plan Projects (JCYJ20140418115815053), Science and Technology Development Project of Shandong Province (jk22), Foundation for Outstanding Young Scientist in Shandong Province (BS2013SW040). Sun Xiulian is the receiver of Taishan Scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.