PMID- 12426310
OWN - NLM
STAT- MEDLINE
DCOM- 20030430
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 7
DP  - 2003 Feb 14
TI  - Characterization of the physical interaction of Gli proteins with SUFU proteins.
PG  - 5116-22
AB  - The Hedgehog signaling pathway is involved in both development and cancer 
      induction in a wide range of organisms. The end point of the Hedgehog 
      signal-transduction cascade is the Gli/Ci, zinc-finger transcription factors. 
      Proteins such as Fused, Suppressor of fused (SUFU), Costal-2, and protein kinase 
      A are essential for regulation of Gli/Ci processing, activity, and localization. 
      Coimmunoprecipitation and Far Western assays, coupled with truncation analysis 
      and mutagenesis have been used to define the region of interaction between Gli 
      proteins and SUFU. We identify a novel motif SYGH in Gli/Ci family proteins, 
      which is required for the interaction with SUFU. Mutational studies revealed that 
      Gly(122) and His(123) are crucial for binding to SUFU, suggesting the importance 
      of hydrophobicity for the correct binding conformation. Functional analysis 
      revealed that the activity of GLI transcription factors with mutations in this 
      motif is no longer suppressed by co-expression of SUFU. Moreover, we have found 
      that a C-terminal 19-amino acid deletion in SUFU (delta465) is sufficient to 
      abrogate interaction with GLI1. Interestingly, this SUFU mutant localizes in the 
      nucleus, most probably because it is not efficiently sequestered in the 
      cytoplasm. Taken together, we identified a novel motif in the Gli/Ci family of 
      proteins that is essential both for protein-protein interaction with SUFU and for 
      functional repression of GLI1 by SUFU.
FAU - Dunaeva, Marina
AU  - Dunaeva M
AD  - Center for Nutrition and Toxicology, Department of Bioscience at NOVUM, 
      Karolinska Institutet, SE-141 57 Huddinge, Sweden.
FAU - Michelson, Piret
AU  - Michelson P
FAU - Kogerman, Priit
AU  - Kogerman P
FAU - Toftgard, Rune
AU  - Toftgard R
LA  - eng
GR  - P01 AR47898-02/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20021107
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Drosophila Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - 0 (cos protein, Drosophila)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 3.6.4.4 (Kinesins)
SB  - IM
MH  - 3T3 Cells
MH  - *Amino Acid Motifs
MH  - Animals
MH  - Binding Sites
MH  - Cell Line
MH  - Cyclic AMP-Dependent Protein Kinases/*chemistry/metabolism
MH  - *Drosophila Proteins
MH  - Humans
MH  - Kinesins/*chemistry/metabolism
MH  - Mice
MH  - Oncogene Proteins/*chemistry/metabolism
MH  - Protein Binding
MH  - Trans-Activators
MH  - Transcription Factors/*chemistry/metabolism
MH  - Zinc Finger Protein GLI1
MH  - Zinc Fingers
EDAT- 2002/11/12 04:00
MHDA- 2003/05/06 05:00
CRDT- 2002/11/12 04:00
PHST- 2002/11/12 04:00 [pubmed]
PHST- 2003/05/06 05:00 [medline]
PHST- 2002/11/12 04:00 [entrez]
AID - S0021-9258(19)32819-4 [pii]
AID - 10.1074/jbc.M209492200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Feb 14;278(7):5116-22. doi: 10.1074/jbc.M209492200. Epub 2002 
      Nov 7.