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-labeling 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 contexts by discovering that XPO1 phosphorylation by STK38 regulates also the nuclear exit of Beclin1 and YAP1, key regulator of autophagy and transcriptional effector, respectively. Collectively, our results reveal STK38 as an activator of XPO1, behaving as a gatekeeper of nuclear export. These observations establish a novel mechanism of XPO1-dependent cargo export regulation by phosphorylation of XPO1's C-terminal auto-inhibitory domain.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Martin AP,Jacquemyn M,Lipecka J,Chhuon C,Aushev VN,Meunier B,Singh MK,Carpi N,Piel M,Codogno P,Hergovich A,Parrini MC,Zalcman G,Guerrera IC,Daelemans D,Camonis JHdoi
10.15252/embr.201948150subject
Has Abstractpub_date
2019-11-05 00:00:00pages
e48150issue
11eissn
1469-221Xissn
1469-3178journal_volume
20pub_type
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