RIO kinase 3 acts as a SUFU-dependent positive regulator of Hedgehog signaling.

Abstract:

:Suppressor of fused (SUFU) is an essential negative regulator of the mammalian Hedgehog (HH) signaling pathway and its loss is associated with cancer development. On a cellular level, endogenous SUFU can mainly be detected in the cytoplasm and the nucleus. However, immunostaining of pancreatic cancer specimen revealed the existence of cell types showing selective enrichment of endogenous SUFU in the nucleus. Following up on this observation, we found that a SUFU construct which was experimentally tethered exclusively to the nucleus was unable to antagonize endogenous HH signaling, in contrast to control SUFU. These data suggest that alterations in the normal subcellular distribution of SUFU might interfere with its established negative role on the HH pathway. Performing a multi-well kinase screen in human cells identified RIO kinase 3 (RIOK3) as a novel modulator of SUFU subcellular distribution. Functionally, RIOK3 acts as a SUFU-dependent positive regulator of HH signaling. Taken together, we propose that factors modulating the nucleo-cytoplasmic distribution of SUFU impact on the normal function of this tumor suppressing protein.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Tariki M,Wieczorek SA,Schneider P,Bänfer S,Veitinger S,Jacob R,Fendrich V,Lauth M

doi

10.1016/j.cellsig.2013.08.037

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

2668-75

issue

12

eissn

0898-6568

issn

1873-3913

pii

S0898-6568(13)00274-X

journal_volume

25

pub_type

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