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Biochem Biophys Res Commun. 2019 May 28;513(2):392-397. doi: 10.1016/j.bbrc.2019.04.010. Epub 2019 Apr 6.

PACT increases mammalian embryonic neural stem cell properties by facilitating activation of the notch signaling pathway.

Author information

1
College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, South Korea.
2
College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, South Korea. Electronic address: keejung@skku.edu.

Abstract

The protein activator of protein kinase R (PKR) (PACT) is known to play important roles in PKR regulation and microRNA biogenesis. Based on the observation that PACT is specifically expressed in the ventricular zone (VZ) at the mid-neurogenic period, we examine the role of PACT in this embryonic neural stem cell niche. Here, we provide the first evidence that PACT increases neurosphere formation, as well as expression of Notch target genes and the neural stem cell marker Sox2 in primary neural stem cells in vitro. Consistently, introduction of PACT into the mouse embryonic brain in utero increased the fraction of cells localizing to the VZ. We also show that the PACT-enhanced stemness of neural stem cells is PKR-independent. At the molecular level, PACT was revealed to physically interact with C promoter binding factor 1 (CBF1) and dramatically strengthen the association between CBF1 and Notch intracellular domain (NICD), which indicates stabilization of the Notch transcriptional coactivation complex responsible for Notch target gene expression. Taken together, our study indicates that PACT is a novel transcriptional coactivator of the Notch pathway playing a pivotal role during mammalian brain development.

KEYWORDS:

Central nervous system development; Neural stem cells; Notch; PACT

PMID:
30967258
DOI:
10.1016/j.bbrc.2019.04.010

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