DYRK1A interacts with Tuberous Sclerosis complex and promotes mTORC1 activity

DYRK1A, which is linked to the dominant intellectual developmental disorder, microcephaly and Down syndrome in humans, regulates numerous cellular processes. Proteomics studeies revealed that DYRK1A interacts with the Tuberous sclerosis complex proteins, namely TSC1 and TSC2, which negatively regulate mTORC1 activation. Biochemical studies demonstrated that DYRK1A phosphorylates TSC2 at T1462, a modification that is known to inhibit Tuberous sclerosis complex activity and promote mTORC1 activity. Further, knockdown of DYRK1A reuslts in reduced cell growth and this phenotype is rescued by overexpression of RHEB, an activator of mTORC1. This results suggest that DYRK1A inhibits TSC complex activity and thereby promotes mTORC1 activity. Further, in Drosophila neuromuscular junction, growth defects caused by the loss of minibrain ( mnb ), the Drosophila homolog of DYRK1A , is rescued by the activation of TORC1 by RHEB overexpression. Overall, the results demonstrate an evolutionarly conserved role of DYRK1A/Mnb in the regulation of TORC1 pathway. ### Competing Interest Statement The authors have declared no competing interest.