| First Author | Ago T | Year | 2008 |
| Journal | Cell | Volume | 133 |
| Issue | 6 | Pages | 978-93 |
| PubMed ID | 18555775 | Mgi Jnum | J:138150 |
| Mgi Id | MGI:3804363 | Doi | 10.1016/j.cell.2008.04.041 |
| Citation | Ago T, et al. (2008) A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy. Cell 133(6):978-93 |
| abstractText | Thioredoxin 1 (Trx1) facilitates the reduction of signaling molecules and transcription factors by cysteine thiol-disulfide exchange, thereby regulating cell growth and death. Here we studied the molecular mechanism by which Trx1 attenuates cardiac hypertrophy. Trx1 upregulates DnaJb5, a heat shock protein 40, and forms a multiple-protein complex with DnaJb5 and class II histone deacetylases (HDACs), master negative regulators of cardiac hypertrophy. Both Cys-274/Cys-276 in DnaJb5 and Cys-667/Cys-669 in HDAC4 are oxidized and form intramolecular disulfide bonds in response to reactive oxygen species (ROS)-generating hypertrophic stimuli, such as phenylephrine, whereas they are reduced by Trx1. Whereas reduction of Cys-274/Cys-276 in DnaJb5 is essential for interaction between DnaJb5 and HDAC4, reduction of Cys-667/Cys-669 in HDAC4 inhibits its nuclear export, independently of its phosphorylation status. Our study reveals a novel regulatory mechanism of cardiac hypertrophy through which the nucleocytoplasmic shuttling of class II HDACs is modulated by their redox modification in a Trx1-sensitive manner. |
