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Genome-wide screening for deubiquitinase subfamily identifies ubiquitin-specific protease 49 as a novel regulator of odontogenesis

Authors
 Kamini Kaushal  ;  Eun-Jung Kim  ;  Apoorvi Tyagi  ;  Janardhan Keshav Karapurkar  ;  Saba Haq  ;  Han-Sung Jung  ;  Kye-Seong Kim  ;  Suresh Ramakrishna 
Citation
 CELL DEATH AND DIFFERENTIATION : epub, 2022-03 
Journal Title
CELL DEATH AND DIFFERENTIATION
ISSN
 1350-9047 
Issue Date
2022-03
Abstract
Proteins expressed by the paired box gene 9 (PAX9) and Msh Homeobox 1 (MSX1) are intimately involved in tooth development (odontogenesis). The regulation of PAX9 and MSX1 protein turnover by deubiquitinating enzymes (DUBs) plausibly maintain the required levels of PAX9 and MSX1 during odontogenesis. Herein, we used a loss-of-function CRISPR-Cas9-mediated DUB KO library kit to screen for DUBs that regulate PAX9 and MSX1 protein levels. We identify and demonstrate that USP49 interacts with and deubiquitinates PAX9 and MSX1, thereby extending their protein half-lives. On the other hand, the loss of USP49 reduces the levels of PAX9 and MSX1 proteins, which causes transient retardation of odontogenic differentiation in human dental pulp stem cells and delays the differentiation of human pluripotent stem cells into the neural crest cell lineage. USP49 depletion produced several morphological defects during tooth development, such as reduced dentin growth with shrunken enamel space, and abnormal enamel formation including irregular mineralization. In sum, our results suggest that deubiquitination of PAX9 and MSX1 by USP49 stabilizes their protein levels to facilitate successful odontogenesis.
Files in This Item:
T202202943.pdf Download
DOI
10.1038/s41418-022-00956-7
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eun-Jung(김은정) ORCID logo https://orcid.org/0000-0002-9515-7590
Jung, Han Sung(정한성) ORCID logo https://orcid.org/0000-0003-2795-531X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/189542
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