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UBE2A/B is the trans-acting factor mediating mechanotransduction and contact inhibition

Mingwei Feng1, Jiale Wang1, Kangjing Li1

  • 1School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, China.

The Biochemical Journal
|October 11, 2023
PubMed

Insights

Researchers identified novel trans-acting factors (TAFs) controlling cell mechanics and contact inhibition. UBE2A/B acts as a key shuttling TAF, mediating a YAP-independent pathway impacting gene expression and cell behavior.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Mechanotransduction and contact inhibition (CI) are crucial for cellular processes like proliferation and differentiation.
  • Identifying downstream trans-acting factors (TAFs) is challenging due to the lack of high-throughput detection methods.

Purpose of the Study:

  • To develop a method for identifying TAFs in open chromatin regions.
  • To detect force- and CI-dependent nucleocytoplasmic shuttling TAFs.
  • To elucidate novel mechanotransduction and CI pathways.

Main Methods:

  • Developed a method combining computational and experimental screening to identify TAFs.
  • Utilized DNaseI-hypersensitive site (DHS) proteomics to discover potential mechanosensing TAFs.
  • Employed next-generation sequencing to analyze downstream gene regulation.

Main Results:

  • Identified over 1000 potential mechanosensing TAFs.
  • Discovered UBE2A/B (Ubiquitin-conjugating enzyme E2 A) as a force- and CI-dependent nucleocytoplasmic shuttling TAF.
  • Demonstrated distinct regulation of YAP/TAZ and UBE2A/B translocation and identified UBE2A/B-mediated histone ubiquitination regulating downstream genes, including YAP.

Conclusions:

  • Established a novel method for TAF identification in open chromatin.
  • Uncovered UBE2A/B as a key mediator in mechanotransduction and CI.
  • Proposed a YAP-independent pathway involving UBE2A/B in regulating gene expression and cellular responses to mechanical cues.
Keywords:
trans-acting factorUBE2Acontact inhibitionmechanotransductionproteomicsubiquitination

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