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Biomolecules. 2019 Apr 17;9(4). pii: E151. doi: 10.3390/biom9040151.

Regulation of the Expression of DAPK1 by SUMO Pathway.

Author information

1
Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China. wangqingshui@fjnu.edu.cn.
2
Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China. 15980239296@163.com.
3
Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China. chenling654321@163.com.
4
Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China. wsy09080700@163.com.
5
Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China. xiayunnyyl@163.com.
6
Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China. m18759141945@163.com.
7
Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China. 13107673087@163.com.
8
Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China. liaoziqiangcontact@163.com.
9
Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China. yb77620@umac.mo.
10
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Dammam, Dammam 31441, Saudi Arabia. kmalsamman@iau.edu.sa.
11
Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China. mmenger@126.com.
12
School of Applied Sciences, Edinburgh Napier University, Edinburgh EH11 4BN, UK. C.Stevens@napier.ac.uk.
13
Institute of Genetics and Molecular Medicine, Cell Signaling Unit, CRUK p53 Transduction Group, University of Edinburgh, EH4 2XR EH4 2XR, UK. ted.hupp@ed.ac.uk.
14
Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China. yaolin@fjnu.edu.cn.

Abstract

Death Associated Protein Kinase 1 (DAPK1) is an important signaling kinase mediating the biological effect of multiple natural biomolecules such as IFN-γ, TNF-α, curcumin, etc. DAPK1 is degraded through both ubiquitin-proteasomal and lysosomal degradation pathways. To investigate the crosstalk between these two DAPK1 degradation pathways, we carried out a screen using a set of ubiquitin E2 siRNAs at the presence of Tuberous Sclerous 2 (TSC2) and identified that the small ubiquitin-like molecule (SUMO) pathway is able to regulate the protein levels of DAPK1. Inhibition of the SUMO pathway enhanced DAPK1 protein levels and the minimum domain of DAPK1 protein required for this regulation is the kinase domain, suggesting that the SUMO pathway regulates DAPK1 protein levels independent of TSC2. Suppression of the SUMO pathway did not enhance DAPK1 protein stability. In addition, mutation of the potential SUMO conjugation sites on DAPK1 kinase domain did not alter its protein stability or response to SUMO pathway inhibition. These data suggested that the SUMO pathway does not regulate DAPK1 protein degradation. The exact molecular mechanism underlying this regulation is yet to be discovered.

KEYWORDS:

DAPK1; SENP; SUMO; post-translational modification; protein degradation

PMID:
30999631
DOI:
10.3390/biom9040151
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