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- Title
UBE2A/B is the trans-acting factor mediating mechanotransduction and contact inhibition.
- Authors
Mingwei Feng; Jiale Wang; Kangjing Li; Fumihiko Nakamura
- Abstract
Mechanotransduction and contact inhibition (CI) control gene expression to regulate proliferation, differentiation, and even tumorigenesis of cells. However, their downstream trans-acting factors (TAFs) are not well known due to a lack of a high-throughput method to quantitatively detect them. Here, we developed a method to identify TAFs on the cisacting sequences that reside in open chromatin or DNaseI-hypersensitive sites (DHSs) and to detect nucleocytoplasmic shuttling TAFs using computational and experimental screening. The DHS-proteomics revealed over 1000 potential mechanosensing TAFs and UBE2A/B (Ubiquitin-conjugating enzyme E2 A) was experimentally identified as a forceand CI-dependent nucleocytoplasmic shuttling TAF. We found that translocation of YAP/ TAZ and UBE2A/B are distinctively regulated by inhibition of myosin contraction, actinpolymerization, and CI depending on cell types. Next-generation sequence analysis revealed many downstream genes including YAP are transcriptionally regulated by ubiquitination of histone by UBE2A/B. Our results suggested a YAP-independent mechanotransduction and CI pathway mediated by UBE2A/B.
- Subjects
CONTACT inhibition; MECHANOTRANSDUCTION (Cytology); NUCLEOCYTOPLASMIC interactions; UBIQUITIN-conjugating enzymes; GENE expression; UBIQUITINATION
- Publication
Biochemical Journal, 2023, Vol 480, Issue 20, p1659
- ISSN
0264-6021
- Publication type
Article
- DOI
10.1042/BCJ20230208