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PMID:17292623

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Citation

Arndt, S, Poser, I, Moser, M and Bosserhoff, AK (2007) Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP signaling. Mol. Cell. Neurosci. 34:603-11

Abstract

The Ski family of nuclear oncoproteins represses transforming growth factor-beta (TGF-beta) signaling through inhibition of transcriptional activity of Smad proteins. In this study, we identified a novel gene, fussel-15 (functional smad suppressing element on chromosome 15) with high homology to the recently discovered Fussel-18 protein. Both, Fussel-15 and Fussel-18, share important structural features, significant homology and similar genomic organization with the homolog Ski family members, Ski and SnoN. Unlike Ski and SnoN, which are ubiquitously expressed in human tissues, Fussel-15 expression, like Fussel-18, is much more restricted in its expression and is principally found in the nervous system of mouse and humans. Interestingly, Fussel-15 expression is even more restricted in adulthood to Purkinje cells of human cerebellum. In contrast to Fussel-18 that interacts with Smad 2, Smad3 and Smad4 and has an inhibitory activity on TGF-beta signaling, Fussel-15 interacts with Smad1, Smad2 and Smad3 molecules and suppresses mainly BMP signaling pathway but has only minor effects on TGF-beta signaling. This new protein expands the family of Ski/Sno proto-oncoproteins and represents a novel molecular regulator of BMP signaling.

Links

PubMed Online version:10.1016/j.mcn.2007.01.002

Keywords

Amino Acid Sequence; Animals; Blotting, Western; Bone Morphogenetic Protein Receptors/metabolism; Cerebellum/metabolism; Fluorescent Antibody Technique; Gene Expression; Gene Expression Profiling; Humans; Immunoblotting; Immunohistochemistry; In Situ Hybridization; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/metabolism; Mice; Molecular Sequence Data; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Purkinje Cells/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Amino Acid; Signal Transduction/physiology; Smad Proteins/metabolism; Transfection; Transforming Growth Factor beta/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SMAD3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P84550

F

Seeded From UniProt

complete

HUMAN:SKOR1

involved_in

GO:0030514: negative regulation of BMP signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SKOR1

located_in

GO:0005634: nucleus

ECO:0000303: author statement without traceable support used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SKOR1

involved_in

GO:0006355: regulation of transcription, DNA-templated

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SKOR1

located_in

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000121)

Seeded From UniProt

complete

HUMAN:SKOR1

located_in

GO:0043025: neuronal cell body

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000121)

Seeded From UniProt

complete

HUMAN:SKOR1

enables

GO:0046332: SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15797

F

Seeded From UniProt

complete

HUMAN:SKOR1

enables

GO:0046332: SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P84022

F

Seeded From UniProt

complete

HUMAN:SKOR1

enables

GO:0046332: SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15796

F

Seeded From UniProt

complete

HUMAN:SMAD2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P84550

F

Seeded From UniProt

complete

HUMAN:SMAD1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P84550

F

Seeded From UniProt

complete


See also

References

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