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
Download URL:
https://stacks.cdc.gov/view/cdc/31385/cdc_31385_DS1.pdf
File Type:

Supporting Files

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