Molecules and Cells

, Volume 27, Issue 1, pp 15–19

Regulation of Notch1/NICD and Hes1 expressions by GSK-3α/β

  • Yun Hye Jin
  • Hangun Kim
  • Minsoo Oh
  • Hyunkyung Ki
  • Kwonseop Kim
Article

Abstract

Notch signaling is controlled at multiple levels. In particular, stabilized Notch receptor activation directly affects the transcriptional activations of Notch target genes. Although some progress has been made in terms of defining the regulatory mechanism that alters Notch stability, it has not been determined whether Notch1/NICD stability is regulated by GSK-3α. Here, we show that Notch1/NICD levels are significantly regulated by GSK-3β and by GSK-3α. Treatment with LiCl (a specific GSK-3 inhibitor) or the overexpression of the kinase-inactive forms of GSK-3α/β significantly increased Notch1/NICD levels. Endogenous NICD levels were also increased by either GSK-3α/β- or GSK-3α-specific siRNA. Furthermore, it was found that GSK-3α binds to Notch1. Deletion analysis showed that at least three Thr residues in Notch1 (Thr-1851, 2123, and 2125) are critical for its response to LiCl, which increased not only the transcriptional activity of endogenous NICD but also Hes1 mRNA levels. Taken together, our results indicate that GSK-3α is a negative regulator of Notch1/NICD.

Keyword

GSK-3 Hes1 LiCl NICD Notch1 

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Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2009

Authors and Affiliations

  • Yun Hye Jin
    • 1
  • Hangun Kim
    • 1
  • Minsoo Oh
    • 1
  • Hyunkyung Ki
    • 1
  • Kwonseop Kim
    • 1
  1. 1.College of Pharmacy and Research Institute of Drug DevelopmentChonnam National UniversityGwangjuKorea

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