PMID- 10564661
OWN - NLM
STAT- MEDLINE
DCOM- 20000203
LR  - 20190524
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 112 ( Pt 23)
DP  - 1999 Dec
TI  - Characterization of the human suppressor of fused, a negative regulator of the
      zinc-finger transcription factor Gli.
PG  - 4437-48
AB  - Drosophila Suppressor of fused (Su(fu)) encodes a novel 468-amino-acid
      cytoplasmic protein which, by genetic analysis, functions as a negative regulator
      of the Hedgehog segment polarity pathway. Here we describe the primary structure,
      tissue distribution, biochemical and functional analyses of a human Su(fu)
      (hSu(fu)). Two alternatively spliced isoforms of hSu(fu) were identified,
      predicting proteins of 433 and 484 amino acids, with a calculated molecular mass 
      of 48 and 54 kDa, respectively. The two proteins differ only by the inclusion or 
      exclusion of a 52-amino-acid extension at the carboxy terminus. Both isoforms
      were expressed in multiple embryonic and adult tissues, and exhibited a
      developmental profile consistent with a role in Hedgehog signaling. The hSu(fu)
      contains a high-scoring PEST-domain, and exhibits an overall 37% sequence
      identity (63% similarity) with the Drosophila protein and 97% sequence identity
      with the mouse Su(fu). The hSu(fu) locus mapped to chromosome 10q24-q25, a region
      which is deleted in glioblastomas, prostate cancer, malignant melanoma and
      endometrial cancer. HSu(fu) was found to repress activity of the zinc-finger
      transcription factor Gli, which mediates Hedgehog signaling in vertebrates, and
      to physically interact with Gli, Gli2 and Gli3 as well as with Slimb, an F-box
      containing protein which, in the fly, suppresses the Hedgehog response, in part
      by stimulating the degradation of the fly Gli homologue. Coexpression of Slimb
      with Su(fu) potentiated the Su(fu)-mediated repression of Gli. Taken together,
      our data provide biochemical and functional evidence for the hypothesis that
      Su(fu) is a key negative regulator in the vertebrate Hedgehog signaling pathway. 
      The data further suggest that Su(fu) can act by binding to Gli and inhibiting
      Gli-mediated transactivation as well as by serving as an adaptor protein, which
      links Gli to the Slimb-dependent proteasomal degradation pathway.
FAU - Stone, D M
AU  - Stone DM
AD  - Departments of Neuroscience, Genentech, Inc. 1 DNA Way, South San Francisco, CA
      94080, USA.
FAU - Murone, M
AU  - Murone M
FAU - Luoh, S
AU  - Luoh S
FAU - Ye, W
AU  - Ye W
FAU - Armanini, M P
AU  - Armanini MP
FAU - Gurney, A
AU  - Gurney A
FAU - Phillips, H
AU  - Phillips H
FAU - Brush, J
AU  - Brush J
FAU - Goddard, A
AU  - Goddard A
FAU - de Sauvage, F J
AU  - de Sauvage FJ
FAU - Rosenthal, A
AU  - Rosenthal A
LA  - eng
SI  - GENBANK/AF144231
SI  - GENBANK/AF159447
SI  - GENBANK/AF222345
PT  - Journal Article
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Drosophila Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SUFU protein, human)
RN  - 0 (Su(fu) protein, Drosophila)
RN  - 0 (Sufu protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Adult
MH  - Alternative Splicing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 10
MH  - Cloning, Molecular
MH  - Drosophila
MH  - *Drosophila Proteins
MH  - Female
MH  - Fetus
MH  - Gene Expression Regulation
MH  - *Gene Expression Regulation, Developmental
MH  - Humans
MH  - Luciferases/genetics
MH  - Male
MH  - Mice
MH  - Molecular Sequence Data
MH  - Oncogene Proteins/*metabolism
MH  - Polymerase Chain Reaction
MH  - Protein Isoforms/genetics/metabolism
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Repressor Proteins/chemistry/*genetics/*metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Trans-Activators
MH  - Transcription Factors/*metabolism
MH  - Zinc Finger Protein GLI1
MH  - Zinc Fingers
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
PST - ppublish
SO  - J Cell Sci. 1999 Dec;112 ( Pt 23):4437-48.