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-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 Rep

journal_title

EMBO reports

authors

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 JH

doi

10.15252/embr.201948150

subject

Has Abstract

pub_date

2019-11-05 00:00:00

pages

e48150

issue

11

eissn

1469-221X

issn

1469-3178

journal_volume

20

pub_type

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