期刊
JOURNAL OF CELL SCIENCE
卷 124, 期 1, 页码 123-132出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.073197
关键词
Actin; Laminin; Microenvironment; Nucleus
类别
资金
- US Dept of Energy
- Office of Biological and Environmental Research [DE-AC02-05CH1123]
- Office of Health and Environmental Research Health Effects Division [03-76SF00098]
- National Cancer Institute [R01CA064786, U54CA126552, U54CA112970, U54CA143836, U01CA143233, R01CA057621]
- US DOD Medical and Materiel Command [W81XWH0810736, W81XWH0510338, W81XWH0410581]
- Canadian Institutes of Health Research
- NATIONAL CANCER INSTITUTE [U54CA143836, U54CA112970, R37CA064786, U54CA126552, R01CA057621, U01CA143233, R01CA064786] Funding Source: NIH RePORTER
Functional differentiation is orchestrated by precise growth-regulatory controls conveyed by the tissue microenvironment. Cues from laminin 111 (LN1) lower transcription and suppress mammary epithelial cell growth in culture, but how LN1 induces quiescence is unknown. Recent literature points to involvement of nuclear beta-actin in transcriptional regulation. Here, we show that quiescence induced by growth factor withdrawal, or LN1 addition, rapidly decreases nuclear beta-actin. LN1, but not other extracellular matrix (ECM) molecules, decreases the levels of nuclear beta-actin and destabilizes RNA polymerase (RNA Pol) II and III binding to transcription sites, leading to a dramatic drop in transcription and DNA synthesis. Constitutive overexpression of globular beta-actin in the nucleus reverses the effect of LN1 on transcription and RNA Pol II association and prevents the cells from becoming quiescent in the presence of LN1. The physiological relevance of our findings was verified by identifying a clear spatial separation of LN1 and beta-actin in developing mammary end buds. These data indicate a novel role for nuclear beta-actin in growth arrest of epithelial cells and underscore the importance of the integrity of the basement membrane in homeostasis.
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