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PMID:25514493

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Citation

Yang, Y, Cui, J, Xue, F, Zhang, C, Mei, Z, Wang, Y, Bi, M, Shan, D, Meredith, A, Li, H and Xu, ZQ (2015) Pokemon (FBI-1) interacts with Smad4 to repress TGF-β-induced transcriptional responses. Biochim. Biophys. Acta 1849:270-81

Abstract

Pokemon, an important proto-oncoprotein, is a transcriptional repressor that belongs to the POK (POZ and Krüppel) family. Smad4, a key component of TGF-β pathway, plays an essential role in TGF-β-induced transcriptional responses. In this study, we show that Pokemon can interact directly with Smad4 both in vitro and in vivo. Overexpression of Pokemon decreases TGF-β-induced transcriptional activities, whereas knockdown of Pokemon increases these activities. Interestingly, Pokemon does not affect activation of Smad2/3, formation of Smads complex, or DNA binding activity of Smad4. TGF-β1 treatment increases the interaction between Pokemon and Smad4, and also enhances the recruitment of Pokemon to Smad4-DNA complex. In addition, we also find that Pokemon recruits HDAC1 to Smad4 complex but decreases the interaction between Smad4 and p300/CBP. Taken together, all these data suggest that Pokemon is a new partner of Smad4 and plays a negative role in TGF-β pathway.

Links

PubMed Online version:10.1016/j.bbagrm.2014.12.008

Keywords

Binding Sites; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Hep G2 Cells; Humans; Protein Interaction Maps/genetics; Signal Transduction/genetics; Smad2 Protein/genetics; Smad2 Protein/metabolism; Smad3 Protein/genetics; Smad3 Protein/metabolism; Smad4 Protein/genetics; Smad4 Protein/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Transcriptional Activation/genetics; Transforming Growth Factor beta/metabolism; Transforming Growth Factor beta/pharmacology

Significance

Annotations

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

HUMAN:SMAD4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O95365

F

Seeded From UniProt

complete

HUMAN:CBP

involved_in

GO:0030511: positive regulation of transforming growth factor beta receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMAD4

involved_in

GO:0007179: transforming growth factor beta receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ZBT7A

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ZBT7A

involved_in

GO:0030512: negative regulation of transforming growth factor beta receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ZBT7A

enables

GO:0046332: SMAD binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ZBT7A

enables

GO:0046332: SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13485

F

Seeded From UniProt

complete

HUMAN:Q4LE28

involved_in

GO:0030511: positive regulation of transforming growth factor beta receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:EP300

involved_in

GO:0030511: positive regulation of transforming growth factor beta receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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