RRC ID 54459
Author Liaw GJ, Chiang CS.
Title Inactive Tlk associating with Tak1 increases p38 MAPK activity to prolong the G2 phase.
Journal Sci Rep
Abstract To guard genome integrity, response mechanisms coordinately execute the G2/M checkpoint in responding to stress. p38 MAPK is activated to prolong the G2 phase for completion of damage repair. Tlk activity is required for DNA repair, chromosome segregation and G2 recovery. However, the involvement of Tlk in G2 recovery differs from previous findings that Tlk overexpression delays the G2/M transition. To clarify this difference, genetic interaction experiments were performed using the second mitotic wave as model system. The results indicate that Tlk overexpression prolongs the G2 phase through p38 MAPK activation, independent of Tlk kinase activity. The results of co-immunoprecipitation, database search and RNAi screening suggest that eEF1α1 and Hsc70-5 links Tlk to Tak1. Reduced gene activities of Tlk, Hsc70-5, eEF1α1 and/or Tak1 couldn't prolong the G2 phase induced by heat shock, indicating that these proteins work together to elevate p38 MAPK activity. In contrast, a high level of wild type Tlk decreases phosphorylated p38 MAPK levels. Thus, the difference is explained by a dual function of Tlk. When under stress, inactive Tlk increases p38 MAPK activity to prolong the G2 phase, and then activated Tlk modulates activities of p38 MAPK and Asf1 to promote G2 recovery afterwards.
Volume 9(1)
Pages 1885
Published 2019-2-13
DOI 10.1038/s41598-018-36137-1
PII 10.1038/s41598-018-36137-1
PMID 30760733
PMC PMC6374402
MeSH Animals Animals, Genetically Modified / metabolism Drosophila / metabolism Drosophila Proteins / antagonists & inhibitors Drosophila Proteins / genetics Drosophila Proteins / metabolism* Embryo, Nonmammalian / metabolism Eye / cytology Eye / metabolism Female G2 Phase Cell Cycle Checkpoints Gene Expression Regulation, Developmental HSC70 Heat-Shock Proteins / antagonists & inhibitors HSC70 Heat-Shock Proteins / genetics HSC70 Heat-Shock Proteins / metabolism MAP Kinase Kinase Kinases / antagonists & inhibitors MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism* Mutagenesis Phosphorylation Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism* RNA Interference RNA, Small Interfering / metabolism p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism*
IF 4.011
Times Cited 1
Drosophila HMS00917 8542R-1 10279R-1 HMS00540 DGRC#203932 DGRC#141749 DGRC#140188