Transcriptional ERRgamma2-mediated activation is regulated by sentrin-specific proteases.
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Transcriptional ERRgamma2-mediated activation is regulated by sentrin-specific proteases. / Hentschke, Moritz; Süsens, Ute; Borgmeyer, Uwe.
In: BIOCHEM J, Vol. 419, No. 1, 1, 2009, p. 167-176.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Transcriptional ERRgamma2-mediated activation is regulated by sentrin-specific proteases.
AU - Hentschke, Moritz
AU - Süsens, Ute
AU - Borgmeyer, Uwe
PY - 2009
Y1 - 2009
N2 - Modification with SUMOs (small ubiquitin-related modifiers) has emerged as an important means of regulating the activity of transcription factors, often by repressing their activity. The ERRgamma [oestrogen receptor-related receptor gamma; ERR3 or NR3B3 (nuclear receptor subfamily 3, group B, gene3)] is a constitutively active orphan nuclear receptor. A PDSM, (phosphorylation-dependent sumoylation motif) is located in the close vicinity of the N-terminally located ERRgamma2-specific AF-1 (activation function-1). Its function can be replaced by an NDSM (negatively charged amino acid-dependent sumoylation motif). A mutational analysis reveals that ERRgamma2 activity is modulated through sumoylation of a lysine residue at position 40, which in turn is regulated by phosphorylation. Phosphorylation at the +5 position relative to the sumoylation target is directly visualized by a high-resolution EMSA (electrophoretic mobility-shift assay). Sumoylation represses the activity of ERRgamma both with and without forced expression of the PGC-1beta (peroxisome-proliferator-activated receptor gamma co-activator-1beta). Fusion proteins of a heterologous DNA-binding domain with the ERRgamma2 N-terminus demonstrate the function of the PDSM as the RF-1 (repression function-1) for the neighbouring AF-1. De-repression is achieved by co-expression of sentrin/SENP (sentrin-specific protease) family members. Together, our results demonstrate reversible phosphorylation-dependent sumoylation as a means to regulate the activity of an orphan nuclear receptor.
AB - Modification with SUMOs (small ubiquitin-related modifiers) has emerged as an important means of regulating the activity of transcription factors, often by repressing their activity. The ERRgamma [oestrogen receptor-related receptor gamma; ERR3 or NR3B3 (nuclear receptor subfamily 3, group B, gene3)] is a constitutively active orphan nuclear receptor. A PDSM, (phosphorylation-dependent sumoylation motif) is located in the close vicinity of the N-terminally located ERRgamma2-specific AF-1 (activation function-1). Its function can be replaced by an NDSM (negatively charged amino acid-dependent sumoylation motif). A mutational analysis reveals that ERRgamma2 activity is modulated through sumoylation of a lysine residue at position 40, which in turn is regulated by phosphorylation. Phosphorylation at the +5 position relative to the sumoylation target is directly visualized by a high-resolution EMSA (electrophoretic mobility-shift assay). Sumoylation represses the activity of ERRgamma both with and without forced expression of the PGC-1beta (peroxisome-proliferator-activated receptor gamma co-activator-1beta). Fusion proteins of a heterologous DNA-binding domain with the ERRgamma2 N-terminus demonstrate the function of the PDSM as the RF-1 (repression function-1) for the neighbouring AF-1. De-repression is achieved by co-expression of sentrin/SENP (sentrin-specific protease) family members. Together, our results demonstrate reversible phosphorylation-dependent sumoylation as a means to regulate the activity of an orphan nuclear receptor.
M3 - SCORING: Zeitschriftenaufsatz
VL - 419
SP - 167
EP - 176
JO - BIOCHEM J
JF - BIOCHEM J
SN - 0264-6021
IS - 1
M1 - 1
ER -