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@ARTICLE{Infante:132650,
author = {P. Infante and R. Faedda and F. Bernardi and F. Bufalieri
and L. Lospinoso Severini and R. Alfonsi and D. Mazzà and
M. Siler and S. Coni and A. Po and M. Petroni and E.
Ferretti and M. Mori and E. De Smaele and G. Canettieri and
C. Capalbo and M. Maroder and I. Screpanti and M. Kool$^*$
and S. Pfister$^*$ and D. Guardavaccaro and A. Gulino and L.
Di Marcotullio},
title = {{I}tch/β-arrestin2-dependent non-proteolytic
ubiquitylation of {S}u{F}u controls {H}edgehog signalling
and medulloblastoma tumorigenesis.},
journal = {Nature Communications},
volume = {9},
number = {1},
issn = {2041-1723},
address = {London},
publisher = {Nature Publishing Group},
reportid = {DKFZ-2018-00310},
pages = {976},
year = {2018},
abstract = {Suppressor of Fused (SuFu), a tumour suppressor mutated in
medulloblastoma, is a central player of Hh signalling, a
pathway crucial for development and deregulated in cancer.
Although the control of Gli transcription factors by SuFu is
critical in Hh signalling, our understanding of the
mechanism regulating this key event remains limited. Here,
we show that the Itch/β-arrestin2 complex binds SuFu and
induces its Lys63-linked polyubiquitylation without
affecting its stability. This process increases the
association of SuFu with Gli3, promoting the conversion of
Gli3 into a repressor, which keeps Hh signalling off.
Activation of Hh signalling antagonises the Itch-dependent
polyubiquitylation of SuFu. Notably, different SuFu
mutations occurring in medulloblastoma patients are
insensitive to Itch activity, thus leading to deregulated Hh
signalling and enhancing medulloblastoma cell growth. Our
findings uncover mechanisms controlling the tumour
suppressive functions of SuFu and reveal that their
alterations are implicated in medulloblastoma
tumorigenesis.},
cin = {B062 / L101},
ddc = {500},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)L101-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29515120},
pmc = {pmc:PMC5841288},
doi = {10.1038/s41467-018-03339-0},
url = {https://inrepo02.dkfz.de/record/132650},
}