Link of Dlk/ZIP kinase to cell apoptosis and tumor suppression.
Death-associated protein kinase (DAPk) family has emerged as a novel subfamily of pro-apoptotic serine/threonine kinase in the last 10 years. Although the functions of DAPk have been well documented, those of other family members remain uncertain. In this work, we characterized the expression pattern of human DAPk like kinase/Zipper interacting protein kinase (Dlk/ZIP kinase) in cancer specimens and cell lines. Dlk expression level was significantly down-regulated in cervical carcinoma cells compared to the surrounding non-tumorous tissues. Overexpression of Dlk led to cell morphological changes, suppressed colony formation and elevated cell apoptosis in cancer cell lines. Both the kinase activity and the cytoplasmic localization were required for its pro-apoptotic tendency. Mechanism exploration revealed that upon serum deprivation, Dlk overexpression could sensitize cells to apoptosis while overexpression of the kinase inactive mutant (Dlk-K42A) was able to rescue apoptotic cell death. Our data thus implicates that Dlk plays a positive role in modulating death-related signaling pathways. Reconstitution of Dlk expression might bring a potential therapeutic approach to cervical carcinoma treatments.
Wu
Yanhua
Y
State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, and Department of Gynecology and Obstetrics, Shanghai First People Hospital, Shanghai 200433, PR China.
Yan
Qin
Q
Zuo
Jie
J
Saiyin
Hexige
H
Jiang
Wenjun
W
Qiao
Shouyi
S
Yu
Long
L
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D045744:Cell Line, Tumor; D064550:Death-Associated Protein Kinases; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D025521:Tumor Suppressor Proteins; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases