THESIS DEFENSE — PUBLIC SEMINAR: CRL4 E3 UBIQUITIN LIGASE PROMOTES NEURAL STEM CELL REACTIVATION

Start Date & Time: 
Tuesday, 16 October, 2018 - 10:00
End Date & Time: 
Tuesday, 16 October, 2018 - 11:00
Venue: 

Training Room 3D, Level 3, Duke-NUS

Speaker Details: 

LY PHUONG THAO
IBM PhD PROGRAM (INTAKE 2014)

Synopsis: 

The ability of neural stem cells (NSCs) to transit between quiescence and reactivation is crucial for tissue homeostasis, but the underlying mechanisms are poorly understood. Drosophila larval NSCs have emerged as a powerful model to study reactivation in vivo. Drosophila Hippo pathway maintains NSC quiescence, but its regulation during brain development remains unknown. Here, we showed that CRL4Mahj/DCAF1, an evolutionarily-conserved E3 ubiquitin ligase, is essential for NSCs to exit from quiescence. We showed that DDB1 and Cullin 4, two key components of CRL4, are intrinsically required for NSC reactivation. We have further identified Mahjong (Mahj/DCAF1) as a substrate receptor of CRL4 in promoting NSC reactivation. Moreover, our results demonstrated that CRL4Mahj forms a protein complex with Warts (Wts/LATS), a core kinase of the Hippo pathway, and that Mahj promotes the ubiquitination of Wts. Genetic analyses support our model that CRL4Mahj promotes NSC reactivation by downregulation of Wts. Given that Cullin4B mutations cause mental retardation in human and that CRL4Mahj/DCAF1 and Wts/LATS are highly conserved, similar mechanisms could happen to regulate quiescence-reactivation in other organisms, including humans.

Thesis Advisor: A/Prof. Wang Hongyan