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PMID: 16421275 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Dual degradation signals control Gli protein stability and tumor formation.

Genes & development ·Vol. 20 ·No. 3 ·2006-02-01 ·Pages 276-81

Huntzicker EG, Estay IS, Zhen H, Lokteva LA, Jackson PK, Oro AE

Abstract

Regulated protein destruction controls many key cellular processes with aberrant regulation increasingly found during carcinogenesis. Gli proteins mediate the transcriptional effects of the Sonic hedgehog pathway, which is implicated in up to 25% of human tumors. Here we show that Gli is rapidly destroyed by the proteasome and that mouse basal cell carcinoma induction correlates with Gli protein accumulation. We identify two independent destruction signals in Gli1, D(N) and D(C), and show that removal of these signals stabilizes Gli1 protein and rapidly accelerates tumor formation in transgenic animals. These data argue that control of Gli protein accumulation underlies tumorigenesis and suggest a new avenue for antitumor therapy.

MeSH Terms
Amino Acid Sequence Animals Carcinoma, Basal Cell/etiology,metabolism Cytoplasm/metabolism Gene Expression Regulation Humans Keratinocytes/cytology,metabolism Mice Mice, Transgenic Molecular Sequence Data Mutation NIH 3T3 Cells Oncogene Proteins/genetics,metabolism Proteasome Endopeptidase Complex/metabolism Signal Transduction/genetics,physiology Trans-Activators Transcription Factors/genetics,metabolism Transfection Xenopus Zinc Finger Protein GLI1
Chemicals
Oncogene Proteins Trans-Activators Transcription Factors Zinc Finger Protein GLI1 Proteasome Endopeptidase Complex
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Huntzicker Erik G
Program in Epithelial Biology, Stanford University, Stanford, California 94305, USA.
Estay Ivette S
Zhen Hanson
Lokteva Ludmila A
Jackson Peter K
Oro Anthony E
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1380906
Published
2006-02-01
Epub
2006-00-18
Pages
276-81
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1361699
Subset
IM
Grants
NIGMS NIH HHS · R01GM60439 · United States
NIAMS NIH HHS · R01 AR054780 · United States
PHS HHS · R01ARO46786 · United States
NIGMS NIH HHS · R01 GM060439 · United States
NIAMS NIH HHS · R01 AR046786 · United States
External Links
PubMed source DOI: 10.1101/gad.1380906 PMC Full Text View journal details
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