PMID- 16229683
OWN - NLM
STAT- MEDLINE
DCOM- 20060324
LR  - 20201113
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 394
IP  - Pt 1
DP  - 2006 Feb 15
TI  - Inhibition of GLI1 gene activation by Patched1.
PG  - 19-26
AB  - Patched1 (PTCH1) is a human tumour suppressor that acts as an HH (Hedgehog) 
      receptor protein and is important for embryonic patterning. PTCH1 mediates its 
      effects through SMO (Smoothened) and represses the expression of HH target genes 
      such as the transcription factor GLI1 (glioma 1) as well as PTCH1. Up-regulation 
      of these genes has been observed in several cancer forms, including basal cell 
      carcinoma, digestive track tumours and small cell lung cancer. The fact that 
      PTCH1 down-regulates its own expression via 'negative feedback' is an important 
      feature in HH signalling, as it keeps the balance between HH and PTCH1 activities 
      that are essential for normal development. In the present study, we provide 
      evidence that a novel mechanism allowing PTCH1 to maintain this balance may also 
      exist. We show that gene activation by GLI1, the transcriptional effector of the 
      pathway, can be down-regulated by PTCH1 without involvement of the canonical 
      cascade of HH signalling events. Specifically, the SMO antagonist cyclopamine has 
      no appreciable effects in blocking this PTCH1-mediated inhibition. Moreover, the 
      negative GLI1 regulator SUFU (Suppressor of Fused) was also found to be 
      dispensable. Additionally, deletion mapping of PTCH1 has revealed that the 
      domains encompassed by amino acids 180-786 and 1058-1210 are of highest 
      significance in inhibiting GLI1 gene activation. This contrasts with the 
      importance of the PTCH1 C-terminal domain for HH signalling.
FAU - Rahnama, Fahimeh
AU  - Rahnama F
AD  - Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden. 
      fahimeh.rahnama@cnt.ki.se
FAU - Shimokawa, Takashi
AU  - Shimokawa T
FAU - Lauth, Matthias
AU  - Lauth M
FAU - Finta, Csaba
AU  - Finta C
FAU - Kogerman, Priit
AU  - Kogerman P
FAU - Teglund, Stephan
AU  - Teglund S
FAU - Toftgard, Rune
AU  - Toftgard R
FAU - Zaphiropoulos, Peter G
AU  - Zaphiropoulos PG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Oncogene Proteins)
RN  - 0 (PTCH1 protein, human)
RN  - 0 (Patched Receptors)
RN  - 0 (Patched-1 Receptor)
RN  - 0 (Ptch1 protein, mouse)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Repressor Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Zinc Finger Protein GLI1)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - COS Cells
MH  - Cell Differentiation
MH  - Cell Line
MH  - Chlorocebus aethiops
MH  - Gene Deletion
MH  - Humans
MH  - Mice
MH  - NIH 3T3 Cells
MH  - Oncogene Proteins/*genetics/metabolism
MH  - Patched Receptors
MH  - Patched-1 Receptor
MH  - Protein Structure, Tertiary
MH  - Protein Transport
MH  - Receptors, Cell Surface/chemistry/genetics/*metabolism
MH  - Receptors, G-Protein-Coupled
MH  - Repressor Proteins
MH  - Trans-Activators
MH  - Transcription Factors/*genetics/metabolism
MH  - *Transcriptional Activation
MH  - Zinc Finger Protein GLI1
PMC - PMC1385998
EDAT- 2005/10/19 09:00
MHDA- 2006/03/25 09:00
PMCR- 2006/08/15
CRDT- 2005/10/19 09:00
PHST- 2005/10/19 09:00 [pubmed]
PHST- 2006/03/25 09:00 [medline]
PHST- 2005/10/19 09:00 [entrez]
PHST- 2006/08/15 00:00 [pmc-release]
AID - BJ20050941 [pii]
AID - bj3940019 [pii]
AID - 10.1042/BJ20050941 [doi]
PST - ppublish
SO  - Biochem J. 2006 Feb 15;394(Pt 1):19-26. doi: 10.1042/BJ20050941.