2. Academic Validation
  3. O-GlcNAc modifications regulate lamin A tail processing

O-GlcNAc modifications regulate lamin A tail processing

  • bioRxiv. 2025 Mar 13:2025.03.11.642699. doi: 10.1101/2025.03.11.642699.
Katherine Augspurger 1 2 3,  Elizabeth Martin 1 2,  Jason Maynard 4,  Kevin Welle 5,  Sina Ghaemmaghami 5 6,  Al Burlingame 4,  Barbara Panning 1,  Abby Buchwalter 3
Affiliations

Affiliations

  • 1 Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, United States.
  • 2 TETRAD Graduate Program, University of California San Francisco, San Francisco, United States.
  • 3 Cardiovascular Research Institute, University of California San Francisco, San Francisco, United States.
  • 4 Department of Pharmaceutical Chemistry, University of University of California San Francisco, San Francisco, United States.
  • 5 Mass Spectrometry Resource Laboratory, University of Rochester, Rochester, New York, United States.
  • 6 Department of Biology, University of Rochester, Rochester, New York, United States.
PMID: 40161616 DOI: 10.1101/2025.03.11.642699
Abstract

Lamin A processing is highly regulated, and necessary for proper assembly of the nuclear lamina facilitating its role in nuclear structure and chromatin organization. Pre-lamin A is first farnesylated, and then a short C-terminal peptide is cleaved to produce mature lamin A. O-GlcNAc Transferase (OGT), a glucose sensitive post-translational modification enzyme, is a potential regulator for lamin A processing. To explore the role of OGT in lamin A biogenesis, we examined the effects of OGT levels and OGT inhibition. Variation in OGT dose or inhibition of its activity did not alter endogenous lamin A abundance or distribution. To more directly test the regulatory effects of O-GlcNAcylation on lamin A, we adapted a tail cleavage assay. Mutation of an OGT binding motif and O-GlcNAc modification sites reduced tail cleavage efficiency, suggesting that O-GlcNAcylation promotes lamin A processing. Our findings add to the understanding of the regulation of lamin A cleavage and identify a potential link between glucose metabolism and lamina biogenesis.

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