Notch transactivates Rheb to maintain the multipotency of TSC-null cells
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Author
Cho, Jun-Hung
Patel, Bhaumik
Bonala, Santosh
Manne, Sasikanth
Zhou, Yan
Vadrevu, Surya K.
Patel, Jalpa
Peronaci, Marco
Ghouse, Shanawaz
Roegiers, Fabrice
Mansouri, Hossein
Markiewski, Maciej M.
White, Brandon
Karbowniczek, Magdalena
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/s41467-017-01845-1Metadata
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Cho, J., B. Patel, S. Bonala, S. Manne, Y. Zhou, S. K. Vadrevu, J. Patel, et al. 2017. “Notch transactivates Rheb to maintain the multipotency of TSC-null cells.” Nature Communications 8 (1): 1848. doi:10.1038/s41467-017-01845-1. http://dx.doi.org/10.1038/s41467-017-01845-1.Abstract
Differentiation abnormalities are a hallmark of tuberous sclerosis complex (TSC) manifestations; however, the genesis of these abnormalities remains unclear. Here we report on mechanisms controlling the multi-lineage, early neuronal progenitor and neural stem-like cell characteristics of lymphangioleiomyomatosis (LAM) and angiomyolipoma cells. These mechanisms include the activation of a previously unreported Rheb-Notch-Rheb regulatory loop, in which the cyclic binding of Notch1 to the Notch-responsive elements (NREs) on the Rheb promoter is a key event. This binding induces the transactivation of Rheb. The identified NRE2 and NRE3 on the Rheb promoter are important to Notch-dependent promoter activity. Notch cooperates with Rheb to block cell differentiation via similar mechanisms in mouse models of TSC. Cell-specific loss of Tsc1 within nestin-expressing cells in adult mice leads to the formation of kidney cysts, renal intraepithelial neoplasia, and invasive papillary renal carcinoma.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705704/pdf/Terms of Use
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