Abstract
Pyridoxal 5′-phosphate (PLP), the biologically active form of vitamin B6, is an important cofactor in amino acid metabolism, and supplementary vitamin B6 has protective effects in many disorders. Other than serving as a cofactor, it can also modulate the activities of steroid hormone receptors and transcription factors. However, the molecular basis of this modulation is unclear. Here, we report that mouse nuclear receptor interacting protein 140 (RIP140) can be modified by PLP conjugation. We mapped the modification site to Lys613 by LC-ESI-MS/MS analysis. This modification enhanced its transcriptional corepressive activity and its physiological function in adipocyte differentiation. We attribute this effect to increased interaction of RIP140 with histone deacetylases and nuclear retention of RIP140. This study uncovers a new physiological role of vitamin B6 in gene regulation by PLP conjugation to a transcriptional coregulator, which represents a new function of an old form of protein post-translational modification that has important biological consequences.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 161-165 |
| Number of pages | 5 |
| Journal | Nature Chemical Biology |
| Volume | 3 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2007 |
Bibliographical note
Funding Information:This work was supported by US National Institutes of Health grants DA11190, DA11806, DK54733, DK60521 and K02-DA13926 to L.-N.W. We also thank the staffs of the Mass Spectrometry Consortium for the Life Sciences, Department of Biochemistry, Molecular Biology and Biophysics at the University of Minnesota, St. Paul for recording the mass spectra, and the staff in L.-N.W.’s lab for their help.