Details:

Alternative Title:
Dev Cell
Publisher's site:
http://dx.doi.org/
Personal Author:
Eisner, Adriana ; Pazyra-Murphy, Maria ; Durresi, Ershela ; Zhou, Pengcheng ; Zhao, Xuesong ; ... More +
Eisner, Adriana ; Pazyra-Murphy, Maria ; Durresi, Ershela ; Zhou, Pengcheng ; Zhao, Xuesong ; Chadwick, Emily C. ; Xu, Pin-Xian ; Hillman, R. Tyler ; Scott, Matthew P. ; Greenberg, Michael E. ; Segal, Rosalind A. ; Less -
Description:
Sonic hedgehog (Shh) signaling is critical in development and oncogenesis, but the mechanisms regulating this pathway remain unclear. Although protein phosphorylation clearly affects Shh signaling, little is known about phosphatases governing the pathway. Here, we conducted a small hairpin RNA (shRNA) screen of the phosphatome and identified Eya1 as a positive regulator of Shh signaling. We find that the catalytically active phosphatase Eya1 cooperates with the DNA-binding protein Six1 to promote gene induction in response to Shh and that Eya1/Six1 together regulate Gli transcriptional activators. We show that Eya1, which is mutated in a human deafness disorder, branchio-oto-renal syndrome, is critical for Shh-dependent hindbrain growth and development. Moreover, Eya1 drives the growth of medulloblastoma, a Shh-dependent hindbrain tumor. Together, these results identify Eya1 and Six1 as key components of the Shh transcriptional network in normal development and in oncogenesis.
Subject:
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Animals
Article
Biomarkers, Tumor
Blotting, Western
Carcinogenesis
Cells, Cultured
Chromatin Immunoprecipitation
Gene Expression Profiling
Hedgehog Proteins
Homeodomain Proteins
Humans
Immunoenzyme Techniques
Immunoprecipitation
Intracellular Signaling Peptides And Proteins
Kruppel-Like Transcription Factors
Medulloblastoma
Mice
Mice, Knockout
Mutation
Nuclear Proteins
Oligonucleotide Array Sequence Analysis
Protein Tyrosine Phosphatases
Real-Time Polymerase Chain Reaction
Receptors, Cell Surface
Reverse Transcriptase Polymerase Chain Reaction
Rhombencephalon
RNA, Messenger
RNA, Small Interfering
Signal Transduction

Source:
Dev Cell. 2015 ; 33(1):22-35.;
Pubmed ID:
25816987
Pubmed Central ID:
PMC4418443
Document Type:
Journal Article ;
Funding:
CA142536/CA/NCI NIH HHS/United States ; DP1000839/DP/NCCDPHP CDC HHS/United States ; NIH NS045500/NS/NINDS NIH HHS/United States ; NIH R01 DK64640/DK/NIDDK NIH HHS/United States ; P01 CA142536/CA/NCI NIH HHS/United States ; ... More +
CA142536/CA/NCI NIH HHS/United States ; DP1000839/DP/NCCDPHP CDC HHS/United States ; NIH NS045500/NS/NINDS NIH HHS/United States ; NIH R01 DK64640/DK/NIDDK NIH HHS/United States ; P01 CA142536/CA/NCI NIH HHS/United States ; R01 DC005824/DC/NIDCD NIH HHS/United States ; R01 NS045500/NS/NINDS NIH HHS/United States ; T32 CA009361/CA/NCI NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; T32CA009361/CA/NCI NIH HHS/United States ; Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:7defee3809177bc604b0ca3a761a2bcd412b781e00f0d54f9a4f4666e8933f49
File Type:

Supporting Files

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