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Regulation of the expression of DAPK1 by SUMO pathway.

Wang, Qingshui; Zhang, Xiuli; Chen, Ling; Weng, Shuyun; Xia, Yun; Ye, Yan; Li, Ke; Liao, Ziqiang; Chen, Pengchen; Alsamman, Khaldoon; Meng, Chen; Stevens, Craig; Hupp, Ted R.; Lin, Yao

Authors

Qingshui Wang

Xiuli Zhang

Ling Chen

Shuyun Weng

Yun Xia

Yan Ye

Ke Li

Ziqiang Liao

Pengchen Chen

Khaldoon Alsamman

Chen Meng

Ted R. Hupp

Yao Lin



Abstract

Death Associated Protein Kinase 1 (DAPK1) is an important signaling kinase mediating the biological e ect of multiple natural biomolecules such as IFN-, TNF- , 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.

Citation

Wang, Q., Zhang, X., Chen, L., Weng, S., Xia, Y., Ye, Y., …Lin, Y. (2019). Regulation of the expression of DAPK1 by SUMO pathway. Biomolecules, 9(4), 151. https://doi.org/10.3390/biom9040151

Journal Article Type Article
Acceptance Date Apr 15, 2019
Online Publication Date Apr 17, 2019
Publication Date Apr 17, 2019
Deposit Date Apr 18, 2019
Publicly Available Date Apr 18, 2019
Journal Biomolecules
Electronic ISSN 2218-273X
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 9
Issue 4
Pages 151
DOI https://doi.org/10.3390/biom9040151
Keywords DAPK1; SUMO; SENP; protein degradation; post-translational modification;
Public URL http://researchrepository.napier.ac.uk/Output/1738558
Contract Date Apr 18, 2019

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