TY - JOUR
T1 - Acetylation of pregnane X receptor protein determines selective function independent of ligand activation
AU - Biswas, Arunima
AU - Pasquel, Danielle
AU - Tyagi, Rakesh Kumar
AU - Mani, Sridhar
N1 - Funding Information:
We would like to acknowledge and thank Dr. David Schecter, Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY for helpful discussions. We also acknowledge Drs. Ronald Evans, Steven Kliewer, Petr Pavek, Peter Mackenzie, Wen Xie for providing us with useful reagents. We thank Drs. Madhukumar Venkatesh and Hongwei Wang for helpful discussions. This work was supported in part by a grant R01CA 127231 (to SM) from NIH as well as Onconova Therapeutics., Inc .
PY - 2011/3/18
Y1 - 2011/3/18
N2 - Pregnane X receptor (PXR), like other members of its class of nuclear receptors, undergoes post-translational modification [PTM] (e.g., phosphorylation). However, it is unknown if acetylation (a major and common form of protein PTM) is observed on PXR and, if it is, whether it is of functional consequence. PXR has recently emerged as an important regulatory protein with multiple ligand-dependent functions. In the present work we show that PXR is indeed acetylated in vivo. SIRT1 (Sirtuin 1), a NAD-dependent class III histone deacetylase and a member of the sirtuin family of proteins, partially mediates deacetylation of PXR. Most importantly, the acetylation status of PXR regulates its selective function independent of ligand activation.
AB - Pregnane X receptor (PXR), like other members of its class of nuclear receptors, undergoes post-translational modification [PTM] (e.g., phosphorylation). However, it is unknown if acetylation (a major and common form of protein PTM) is observed on PXR and, if it is, whether it is of functional consequence. PXR has recently emerged as an important regulatory protein with multiple ligand-dependent functions. In the present work we show that PXR is indeed acetylated in vivo. SIRT1 (Sirtuin 1), a NAD-dependent class III histone deacetylase and a member of the sirtuin family of proteins, partially mediates deacetylation of PXR. Most importantly, the acetylation status of PXR regulates its selective function independent of ligand activation.
KW - Acetylation-deacetylation
KW - Ligand-independent function
KW - Orphan nuclear receptor
KW - Pregnane X receptor
KW - SIRT1 deacetylase
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U2 - 10.1016/j.bbrc.2011.02.048
DO - 10.1016/j.bbrc.2011.02.048
M3 - Article
C2 - 21329659
AN - SCOPUS:79952735386
SN - 0006-291X
VL - 406
SP - 371
EP - 376
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -