STK38 kinase acts as XPO1 gatekeeper regulating the nuclear export of autophagy proteins and other cargoes

ABSTRACT: STK38 (also known as NDR1) is a Hippo pathway serine/threonine protein kinase with multifarious functions in normal and cancer cells. Using a context-dependent proximity-labelling assay, we identify more than 250 partners of STK38 and find that STK38 modulates its partnership depending on the cellular context by increasing its association with cytoplasmic proteins upon nutrient starvation-induced autophagy and with nuclear ones during ECM detachment. We show that STK38 shuttles between the nucleus and the cytoplasm and that its nuclear exit depends on both XPO1 (aka Exportin-1, CRM1) and STK38 kinase activity. We further uncover that STK38 modulates XPO1 export activity by phosphorylating XPO1 on serine 1055, thus regulating its own nuclear exit. We expand our model to other cellular conte

SUBMITTER: Dr. Alexandre, PJ Martin 

PROVIDER: S-SCDT-EMBOR-2019-48150V1 | biostudies-other |

REPOSITORIES: biostudies-other