Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-28645

Mosimann, C; Hausmann, G; Basler, K (2009). The role of Parafibromin/Hyrax as a nuclear Gli/Ci-interacting protein in Hedgehog target gene control. Mechanisms of Development, 126(5-6):394-405.

[img] PDF - Registered users only
3MB

View at publisher

Abstract

The Hedgehog (Hh) pathway, an evolutionarily conserved key regulator of embryonic patterning and tissue homeostasis, controls its target genes by managing the processing and activities of the Gli/Ci transcription factors. Little is known about the nuclear co-factors the Gli/Ci proteins recruit, and how they mechanistically control Hh target genes. Here, we provide evidence for the involvement of Parafibromin/Hyx as a positive component in Hh signaling. We found that hyx RNAi impaired Hh pathway activity in Drosophila cell culture. Consistent with an evolutionarily conserved function in Hh signaling, RNAi-mediated knockdown of Parafibromin in mammalian cell culture experiments diminished the transcriptional activity of Gli1 and Gli2. In vivo, in Drosophila, genetic impairment of hyx decreased the expression of the high-threshold Hh target gene knot/collier. Conversely, hyx overexpression ameliorated the inhibitory activity of Ptc and Ci(75) misexpression during Drosophila wing development. We subsequently found that Parafibromin can form a complex with all three Glis, and provide evidence that Parafibromin/Hyx directly binds Region 1, the Su(fu) interaction domain, in the N-terminus of all Glis and Ci. Taken together, our results suggest a target gene-selective involvement of the PAF1 complex in Hh signaling via the Parafibromin/Hyx-mediated recruitment to Gli/Ci.

Citations

12 citations in Web of Science®
12 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

1 download since deposited on 30 Jan 2010
0 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
DDC:570 Life sciences; biology
Language:English
Date:2009
Deposited On:30 Jan 2010 16:11
Last Modified:27 Nov 2013 20:43
Publisher:Elsevier
ISSN:0925-4773
Publisher DOI:10.1016/j.mod.2009.02.002
PubMed ID:19368795

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page