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PMID:18426905

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Citation

Roukens, MG, Alloul-Ramdhani, M, Moghadasi, S, Op den Brouw, M and Baker, DA (2008) Downregulation of vertebrate Tel (ETV6) and Drosophila Yan is facilitated by an evolutionarily conserved mechanism of F-box-mediated ubiquitination. Mol. Cell. Biol. 28:4394-406

Abstract

The vertebrate Ets transcriptional repressor Tel (ETV6) and its invertebrate orthologue, Yan, are both indispensable for development, and they orchestrate cell growth and differentiation by binding to DNA, thus inhibiting gene expression. To trigger cell differentiation, these barriers to transcriptional activation must be relieved, and it is established that posttranslational modifications, such as phosphorylation and sumoylation, can specifically impair the repressive functions of Tel and Yan and are crucial for modulating their transcriptional activity. To date, however, relatively little is known about the control of Tel and Yan protein degradation. In recent years, there has been a concentrated effort to assign functions to the large number of F-box proteins encoded by both vertebrate and invertebrate genomes. Here, we report the identification and characterization of a previously unreported, evolutionarily conserved F-box protein named Fbl6. We isolated both human and Drosophila melanogaster fbl6 cDNA and show that the encoded Fbl6 protein binds to both Tel and Yan via their SAM domains. We demonstrate that both Tel and Yan are ubiquitinated, a process which is stimulated by Fbl6 and leads to proteasomal degradation. We recently established that the sumoylation of Tel on lysine 11 negatively regulates its repressive function and that the sumoylation of Tel monomers, but not that of Tel oligomers, may sensitize Tel for proteasomal degradation. Here, we found that Fbl6 regulates Tel/Yan protein stability and allows appropriate spatiotemporal control of gene expression by these repressors.

Links

PubMed PMC2447152 Online version:10.1128/MCB.01914-07

Keywords

Animals; Cell Line, Tumor; Conserved Sequence; Down-Regulation; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/metabolism; Evolution, Molecular; Eye Proteins/genetics; F-Box Proteins/metabolism; Humans; Protein Binding; Protein Structure, Tertiary; Proto-Oncogene Proteins c-ets/chemistry; Proto-Oncogene Proteins c-ets/genetics; Repressor Proteins/chemistry; Repressor Proteins/genetics; Sequence Homology, Amino Acid; Ubiquitination

Significance

Annotations

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

DROME:POK

enables

GO:0019904: protein domain specific binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0033609

F

Seeded From UniProt

complete

DROME:Q494G8

involved_in

GO:0031647: regulation of protein stability

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q494G8

involved_in

GO:2000060: positive regulation of ubiquitin-dependent protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q494G8

located_in

GO:0005654: nucleoplasm

ECO:0000250: sequence similarity evidence used in manual assertion

HGNC:13603

C

Seeded From UniProt

complete

DROME:Q494G8

enables

GO:0032093: SAM domain binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0000097

F

Seeded From UniProt

complete

DROME:Q961T2

involved_in

GO:0031647: regulation of protein stability

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q961T2

involved_in

GO:2000060: positive regulation of ubiquitin-dependent protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q961T2

located_in

GO:0005654: nucleoplasm

ECO:0000250: sequence similarity evidence used in manual assertion

HGNC:13603

C

Seeded From UniProt

complete

DROME:Q961T2

enables

GO:0032093: SAM domain binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0000097

F

Seeded From UniProt

complete


See also

References

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