Abstract
While Nkx3.2/Bapx1 promotes chondrogenic differentiation and plays a role in maintaining chondrocyte viability and suppressing chondrocyte hypertrophy, the regulatory mechanisms of Nkx3.2 remain poorly understood. Here we show that p300- and HDAC9-induced Nkx3.2 acetylation and de-acetylation, respectively, play critical roles in controlling Nkx3.2 protein stability. In addition, we also found that HDAC9-dependent de-acetylation of Nkx3.2 triggers PIASy-mediated sumoylation and subsequent RNF4-mediated SUMO-targeted ubiquitination. Furthermore, we demonstrate that Nkx3.2 regulation by HDAC9 can be linked to the management of chondrocyte survival and hypertrophic maturation during cartilage development. Finally, our results together reveal a novel mechanism of protein stability control involving complex interplay between acetylation, de-acetylation, sumoylation, and ubiquitination, and suggest that this post-translational modification of Nkx3.2 employing HDAC9-PIASy-RNF4 axis plays a crucial role in controlling chondrocyte viability and hypertrophic maturation during skeletal development in vertebrates.
Original language | English |
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Pages (from-to) | 1336-1348 |
Number of pages | 13 |
Journal | Cellular Signalling |
Volume | 28 |
Issue number | 9 |
DOIs | |
Publication status | Published - 2016 Sep 1 |
Bibliographical note
Funding Information:This work was supported by the grants ( NRF-2012M3A9A9055078 ; 2015K000180 ) funded by the Korean Ministry of Science, ICT and Future Planning .
Publisher Copyright:
© 2016 Elsevier Inc.
All Science Journal Classification (ASJC) codes
- Cell Biology