2. Academic Validation
  3. Proteolytic processing of secretory pathway kinase Fam20C by site-1 protease promotes biomineralization

Proteolytic processing of secretory pathway kinase Fam20C by site-1 protease promotes biomineralization

  • Proc Natl Acad Sci U S A. 2021 Aug 10;118(32):e2100133118. doi: 10.1073/pnas.2100133118.
Xinxin Chen 1 2,  Jianchao Zhang 1 2,  Pulan Liu 3,  Yangyang Wei 3,  Xi'e Wang 1,  Junyu Xiao 3,  Chih-Chen Wang 1 2,  Lei Wang 4 2
Affiliations

Affiliations

  • 1 National Laboratory of Biomacromolecules, Chinese Academy of Sciences (CAS) Center for Excellence in Biomacromolecules, Institute of Biophysics, CAS, Beijing 100101, China.
  • 2 College of Life Sciences, University of CAS, Beijing 100049, China.
  • 3 The State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
  • 4 National Laboratory of Biomacromolecules, Chinese Academy of Sciences (CAS) Center for Excellence in Biomacromolecules, Institute of Biophysics, CAS, Beijing 100101, China; [email protected].
PMID: 34349020 DOI: 10.1073/pnas.2100133118
Abstract

Family with sequence similarity 20C (Fam20C), the major protein kinase in the secretory pathway, generates the vast majority of the secreted phosphoproteome. However, the regulatory mechanisms of Fam20C transport, secretion, and function remain largely unexplored. Here, we show that Fam20C exists as a type II transmembrane protein within the secretory compartments, with its N-terminal signal peptide-like region serving as a membrane anchor for Golgi retention. The secretion and kinase activity of Fam20C are governed by site-1 protease (S1P), a key regulator of Cholesterol homeostasis. We find that only mature Fam20C processed by S1P functions in osteoblast differentiation and mineralization. Together, our findings reveal a unique mechanism for Fam20C secretion and activation via proteolytic regulation, providing a molecular link between biomineralization and lipid metabolism.

Keywords

Fam20C; Golgi; phosphorylation; proteolysis; site-1 protease.

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