RRC ID 51764
Author Choi HJ, Kwon S, Kim DW.
Title A post-translational modification cascade employing HDAC9-PIASy-RNF4 axis regulates chondrocyte hypertrophy by modulating Nkx3.2 protein stability.
Journal Cell Signal
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.
Volume 28(9)
Pages 1336-48
Published 2016-9-1
DOI 10.1016/j.cellsig.2016.06.006
PII S0898-6568(16)30140-1
PMID 27312341
MeSH Acetylation Animals Cell Line Cell Survival Chondrocytes / metabolism Chondrocytes / pathology* Histone Deacetylase 1 / metabolism Histone Deacetylases / metabolism* Homeodomain Proteins / metabolism* Humans Hypertrophy Lysine / metabolism Mice, Inbred C57BL Models, Biological Nuclear Proteins / metabolism* Poly-ADP-Ribose Binding Proteins / metabolism* Protein Inhibitors of Activated STAT / metabolism* Protein Processing, Post-Translational* Protein Stability Repressor Proteins / metabolism* Signal Transduction* Sumoylation Transcription Factors / metabolism* Ubiquitination
IF 3.388
Times Cited 4
Human and Animal Cells ATDC5(RCB0565)