PgmNr D1067: Tousled-like kinase regulates G2/M transition through Tak1 to activate p38a MAPK.

Authors:
G. Liaw


Institutes
Natl Yang-Ming Univ, Taipei, TW.


Keyword: checkpoint

Abstract:

To maintain genome integrity, cell-cycle checkpoints are monitoring DNA damages and abnormal chromosome segregation caused by environmental stresses. Numerous studies have demonstrated that Tousled-like kinase (Tlk) activity is required for the faithful segregation of chromosomes and the DNA repair. Previous studies show that tlk overexpression delays G2/M transition. The delay is relieved by reduced p38a activity, consistent with both Tlk and p38a activities required for stalling G2/M transition under heat shock. Phosphorylation of p38 is significantly increased by overexpressed kinase-dead Tlk (TlkKD), suggesting that Tlk is a cofactor of a kinase that activates p38a. To find the kinase, proteins in Tlk co-immunoprecipitated complexes are identified by mass spectrometry. Using the esyN program, I find four identified proteins, Rm62, MEP-1, Hsc70-5 and EF1a48D that directly or indirectly link to Tak1. The TlkKD-facilitated p38 phosphorylation is abolished by removing Tak1 activity, consistent with both Tlk and Tak1 activities required for stalling G2/M transition under heat shock. Similarly, responding to heat shock, G2/M transition is unstoppable in eye discs with reduced two gene activities among EF1a48D, Hsc70-5, Tak1 and Tlk. Taken together, Tlk acts as a positive mediator of Tak1 that activates p38a to delay G2/M transition induced by either Tlk overexpression or heat shock. Tlk activity likely coordinate G2/M checkpoint and responses to environmental insults to maintain genome integrity.



Flybase Genetic Index:
1. FlyBase gene symbol: Dmel\Tlk; FBgn: FBgn0086899
2. FlyBase gene symbol: Dmel\p38a; FBgn: FBgn0015765
3. FlyBase gene symbol: Dmel\Tak1; FBgn: FBgn0026323
4. FlyBase gene symbol: Dmel\Hsc70-5; FBgn: FBgn0001220
5. FlyBase gene symbol: Dmel\Ef1α48D; FBgn: FBgn0000556