Year: 2019
Type: article
Abstract: ULK1, the upper-most protein of the ULK1 complex, is emerging as a crucial node in autophagy induction. However, the regulation of ULK1 is not fully understood. In this study, we identified TOPK (T-LAK cell-originated protein kinase), an oncokinase, as a novel upstream kinase to phosphorylate ULK1. We found that TOPK could directly bind with and phosphorylate ULK1 at Ser469, Ser495, and Ser533. The phosphorylation of ULK1 at Ser469, Ser495, and Ser533 by TOPK decreased the activity and stability of ULK1. In addition, we want to examine the initiation of autophagy because the reduction activity of ULK1 reduces the occurrence of autophagy. We demonstrated that TOPK could inhibit the initiation and progression of autophagy in glioma cells. Furthermore, TOPK inhibition increased the sensitivity of glioma cells to temozolomide (TMZ). This discovery provides insight into the problem of TMZ-resistance in GBM treatment.
Source: Cell Death and Disease
Authors: Hui Lu, Juanjuan Xiao, Changshu Ke, Xiaofang Ni, Ruijuan Xiu, Qin Tian, Huaxiong Pan, Ling Zou, Fei Wang, Tengfei Ma, Xinying Ji, Ping Yuan, Lin Liu, Jianmin Zhang, Wei Jia, Qiuhong Duan, Feng Zhu
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,760
OpenAlex ID: W2964356325