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Phosphorylation-dependent sumoylation of estrogen-related receptor alpha1.

Abstract：

:We previously showed that estrogen-related receptor alpha1 (ERRalpha1) can compete with estrogen receptor alpha (ERalpha) for binding to estrogen response elements (EREs), repressing transcription in the mammary carcinoma cell line MCF-7. Given that ERRalpha1 can function in the absence of ligands and exists as a phosphoprotein in vivo, we wished to determine sites of phosphorylation involved in regulating its transcriptional activity. Using a combination of electrophoretic mobility shift analysis, phospho-specific fluorescent dye staining, and site-directed mutagenesis, we identified two novel in vivo sites of phosphorylation in the A/B ligand-independent activation domain of ERRalpha1 at Ser19 and Ser22. Inhibition of phosphorylation at amino acid residue 22 did not have a significant effect on ERRalpha1's transcriptional activity. However, mutation of amino acid residue 19 from serine to alanine enhanced two-fold ERRalpha1's response to the coactivator GRIP-1. We also identified two sites of sumoylation at Lys14 and Lys403. We found that inhibition of sumoylation at Lys14 could enhance five-fold ERRalpha1's response to coactivator GRIP-1. Furthermore, phosphorylation of Ser19 enhanced the sumoylation at Lys14. Taken together, we conclude that phosphorylation at Ser19 and sumoylation at Lys14 within the A/B domain play roles in regulating ERRalpha1's transcriptional activities via affecting its response to coactivators.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Vu EH,Kraus RJ,Mertz JE

doi

10.1021/bi700316g

subject

Has Abstract

pub_date

2007-08-28 00:00:00

pages

9795-804

issue

34

eissn

0006-2960

issn

1520-4995

journal_volume

46

pub_type

杂志文章

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