Integrin-linked kinase controls Notch1 signaling by down-regulation of protein stability through Fbw7 ubiquitin ligase

Mo Jung-Soon, Kim Mi-Yeon, Han Seung-Ok, Kim In-Sook, Ann Eun-Jung, Shik Lee Kyu, Seo Mi-Sun, Kim Jin-Young, Lee Hee-Sae, Park Jeen-Woo, Eui Ju Choi, Jae Young Seong, Joe O. Cheol, Faessler Reinhard, Park Hee-Sae

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Integrin-linked kinase (ILK) is a scaffold and protein kinase that acts as a pivotal effector in integrin signaling for various cellular functions. In this study, we found that ILK remarkably reduced the protein stability of Notch1 through Fbw7. The kinase activity of ILK was essential for the inhibition of Notch1 signaling. Notably, the protein level and transcriptional activity of the endogenous Notch1 intracellular domain (Notch1-IC) were higher in ILK-null cells than in ILK wild-type cells, and the level of endogenous Notch1-IC was increased by the blocking of the proteasome, suggesting that ILK enhances the proteasomal degradation of Notch1-IC. ILK directly bound and phosphorylated Notch1-IC, thereby facilitating proteasomal protein degradation through Fbw7. Furthermore, we found down-regulation of Notch1-IC and up-regulation of ILK in basal cell carcinoma and melanoma patients but not in squamous cell carcinoma patients. These results suggest that ILK down-regulated the protein stability of Notch1-IC through the ubiquitin-proteasome pathway by means of Fbw7.

Original languageEnglish
Pages (from-to)5565-5574
Number of pages10
JournalMolecular and Cellular Biology
Volume27
Issue number15
DOIs
Publication statusPublished - 2007 Aug 1

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Protein Stability
Ligases
Ubiquitin
Down-Regulation
Proteasome Endopeptidase Complex
integrin-linked kinase
Null Lymphocytes
Basal Cell Carcinoma
Integrins
Protein Kinases
Proteolysis
Squamous Cell Carcinoma
Melanoma
Phosphotransferases
Up-Regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Jung-Soon, M., Mi-Yeon, K., Seung-Ok, H., In-Sook, K., Eun-Jung, A., Kyu, S. L., ... Hee-Sae, P. (2007). Integrin-linked kinase controls Notch1 signaling by down-regulation of protein stability through Fbw7 ubiquitin ligase. Molecular and Cellular Biology, 27(15), 5565-5574. https://doi.org/10.1128/MCB.02372-06

Integrin-linked kinase controls Notch1 signaling by down-regulation of protein stability through Fbw7 ubiquitin ligase. / Jung-Soon, Mo; Mi-Yeon, Kim; Seung-Ok, Han; In-Sook, Kim; Eun-Jung, Ann; Kyu, Shik Lee; Mi-Sun, Seo; Jin-Young, Kim; Hee-Sae, Lee; Jeen-Woo, Park; Choi, Eui Ju; Seong, Jae Young; Cheol, Joe O.; Reinhard, Faessler; Hee-Sae, Park.

In: Molecular and Cellular Biology, Vol. 27, No. 15, 01.08.2007, p. 5565-5574.

Research output: Contribution to journalArticle

Jung-Soon, M, Mi-Yeon, K, Seung-Ok, H, In-Sook, K, Eun-Jung, A, Kyu, SL, Mi-Sun, S, Jin-Young, K, Hee-Sae, L, Jeen-Woo, P, Choi, EJ, Seong, JY, Cheol, JO, Reinhard, F & Hee-Sae, P 2007, 'Integrin-linked kinase controls Notch1 signaling by down-regulation of protein stability through Fbw7 ubiquitin ligase', Molecular and Cellular Biology, vol. 27, no. 15, pp. 5565-5574. https://doi.org/10.1128/MCB.02372-06
Jung-Soon, Mo ; Mi-Yeon, Kim ; Seung-Ok, Han ; In-Sook, Kim ; Eun-Jung, Ann ; Kyu, Shik Lee ; Mi-Sun, Seo ; Jin-Young, Kim ; Hee-Sae, Lee ; Jeen-Woo, Park ; Choi, Eui Ju ; Seong, Jae Young ; Cheol, Joe O. ; Reinhard, Faessler ; Hee-Sae, Park. / Integrin-linked kinase controls Notch1 signaling by down-regulation of protein stability through Fbw7 ubiquitin ligase. In: Molecular and Cellular Biology. 2007 ; Vol. 27, No. 15. pp. 5565-5574.
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