The homeoprotein Msx1 cooperates with Pkn1 to prevent terminal differentiation in myogenic precursor cells

• Published in: Biochimie 2019-07, Vol.162, p.55-65
• Main Authors: Zhu, Xiaoli, Li, Mingrui, Jia, Xiang, Hou, Wanwan, Yang, Jiange, Zhao, Hui, Wang, Gang, Wang, Jingqiang
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation; Gene Expression Regulation, Developmental; HEK293 Cells; Humans; Mice; Msx1; MSX1 Transcription Factor - metabolism; Muscle Development; Myf5; Myoblasts, Skeletal - cytology; Myoblasts, Skeletal - physiology; myogenic differentiation; Myogenic Regulatory Factor 5 - genetics; Myogenic Regulatory Factor 5 - metabolism; Pkn1; Promoter Regions, Genetic; Protein Kinase C - genetics; Protein Kinase C - metabolism
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2019.04.003

The homeoprotein Msx1 plays a critical role in embryonic patterning, particularly to maintain myogenic progenitor cell fate. However, the mechanisms underlying Msx1-mediated inhibition of myogenesis remain largely unknown. Here, we show that Msx1 cooperates with the protein kinase C-related kinase 1 (Pkn1), a member of the protein kinase C-related kinase family, to prevent the terminal differentiation of myogenic precursor cells. In mouse C2C12 cells, Pkn1 knockout partly impaired Msx1-mediated inhibition of myogenic differentiation, indicating a role for Pkn1 in this process. Furthermore, we found that Pkn1 was required for Msx1 enrichment at the promoter of Myf5, a myogenic regulatory gene. In Pkn1 knockout cells, this reduced Msx1 enrichment at the Myf5 promoter coincided with attenuated repression of Myf5 transcription. Together with our observation that Msx1 and Pkn1 were associated in a protein complex, these findings strongly suggest that Msx1 cooperates with Pkn1 to down-regulate Myf5 and, therefore, prevent the differentiation of myogenic precursor cells. Collectively, our data provide key insights into the mechanisms underlying Msx1 function in the prevention of myogenic differentiation. •Msx1 cooperates with Pkn1 to prevent the differentiation of myogenic precursor cells.•Msx1 cooperates with Pkn1 to promote cell proliferation.•Pkn1 cooperates with Msx1 to inhibit Myf5 expression.•Pkn1 drives Msx1 localisation to the nuclear periphery.