Unknown

Dataset Information

0

Notch transactivates Rheb to maintain the multipotency of TSC-null cells.


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.

SUBMITTER: Cho JH 

PROVIDER: S-EPMC5705704 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications


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-res  ...[more]

Similar Datasets

| S-EPMC2798691 | biostudies-literature
| S-EPMC7804450 | biostudies-literature
| S-EPMC9497210 | biostudies-literature
| S-EPMC6529079 | biostudies-literature
| S-EPMC6035085 | biostudies-literature
| S-EPMC3179115 | biostudies-literature
| S-EPMC6611768 | biostudies-literature
| S-EPMC2896794 | biostudies-literature
| S-EPMC5907840 | biostudies-other
| S-EPMC5431284 | biostudies-literature