Protein N-Terminomics Reveals Major Proteases in Regulating Beige Adipocyte Differentiation

ABSTRACT: We have developed an analytical platform to measure the temporal profiles of the proteome and the protein N-terminome during beige adipocyte differentiation. Our recently developed N-terminomics approach was applied to isolate protein N-terminal peptides with up to 97% purity. In total, we identified 7,171 unique N- terminal peptides, of which 3,043 were from canonical proteins (CanNt peptides) and 4,129 were from proteins with neo-N-termini (NeoNt peptides). We found that 44% of proteins showed different temporal profiles between the global proteome and protein N-terminome. Our results indicate that proteolysis plays a major role in regulating beige adipocyte differentiation. Knockdown of Pmpbc, Plg or Cstd in preadipocytes impeded thermogenesis by decreasing Cidea, Pgc1a and Ucp1 expression and elevating adipogenic markers such as Fasn and Fabp4, thus promoting the beige-to-white adipocyte transition. Our approach reveals that proteases and the generated proteolysis products play major roles in beige adipocyte differentiation.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Yasushi Ishihama 

PROVIDER: PXD045109 | JPOST Repository | Fri Sep 05 00:00:00 BST 2025

REPOSITORIES: jPOST