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SIPAR negatively regulates STAT3 signaling and inhibits progression of melanoma
- Source :
- Cellular signalling. 25(11)
- Publication Year :
- 2013
-
Abstract
- Persistently activated STAT3 is important for tumorigenesis in a variety of cancers, including melanoma. Although many co-factors in the regulation of STAT3 activity have been identified, it remains unclear how STAT3 phosphorylation is negatively regulated. Here, we report that SIPAR (STAT3-Interacting Protein As a Repressor) inhibits STAT3 activity by accelerating its dephosphorylation. We observed that SIPAR directly interacted with STAT3 upon IL-6 stimulation. Moreover, over-expression of SIPAR reduced, whereas depletion enhanced, the level of phosphorylated STAT3. We further demonstrated that SIPAR inhibited the growth of melanoma cells by decreasing the level of phosphorylated STAT3 and the expression of its target genes. These results suggest that SIPAR, functioning as a new negative regulator, inhibits STAT3 activity by enhancing its dephosphorylation and represses melanoma progression.
- Subjects :
- Male
STAT3 Transcription Factor
Skin Neoplasms
Molecular Sequence Data
Melanoma, Experimental
Repressor
Mice, Nude
Stimulation
medicine.disease_cause
Dephosphorylation
Mice
Genes, Reporter
Cell Line, Tumor
medicine
Animals
Humans
Amino Acid Sequence
Phosphorylation
STAT3
Luciferases
Gene
Adaptor Proteins, Signal Transducing
biology
Sequence Homology, Amino Acid
Interleukin-6
Melanoma
Nuclear Proteins
Cell Biology
medicine.disease
Tumor Burden
Gene Expression Regulation, Neoplastic
Cancer research
biology.protein
Disease Progression
NIH 3T3 Cells
Carcinogenesis
Signal Transduction
Subjects
Details
- ISSN :
- 18733913
- Volume :
- 25
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Cellular signalling
- Accession number :
- edsair.doi.dedup.....ff06b72c54d8d2a9d50df51b77bac439