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

Abstract

Death Associated Protein Kinase 1 (DAPK1) is an important signaling kinase mediating the biological eect 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.

• 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