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 Signaljournal_title
Cellular signallingauthors
Tariki M,Wieczorek SA,Schneider P,Bänfer S,Veitinger S,Jacob R,Fendrich V,Lauth Mdoi
10.1016/j.cellsig.2013.08.037subject
Has Abstractpub_date
2013-12-01 00:00:00pages
2668-75issue
12eissn
0898-6568issn
1873-3913pii
S0898-6568(13)00274-Xjournal_volume
25pub_type
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