PKR-mediated degradation of STAT1 regulates osteoblast differentiation

Kaya Yoshida, Hirohiko Okamura, Bruna Rabelo Amorim, Daisuke Hinode, Hideo Yoshida, Tatsuji Haneji

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The double-stranded RNA-dependent protein kinase (PKR) plays a critical role in various biological responses including antiviral defense, cell differentiation, apoptosis, and tumorigenesis. In this study, we investigated whether PKR could affect the post-translational modifications of STAT1 protein and whether these modifications regulate osteoblast differentiation. We demonstrated that PKR was necessary for the ubiquitination of STAT1 protein. The expressions of bone-related genes such as type I collagen, integrin binding sialoprotein, osteopontin, and osterix were suppressed in osteoblasts lacking PKR activity. In contrast, the expressions of interleukin-6 and matrix metalloproteinases 8 and 13 increased in PKR-mutated osteoblasts. The expression and degradation of STAT1 protein were regulated by PKR in a SLIM-dependent pathway. Inhibition of SLIM by RNA interference resulted in the decreased activity of Runx2 in osteoblasts. Stimulation of interleukin-6 expression and suppression of alkaline phosphatase activity were regulated through by SLIM-dependent pathway. However, expressions of bone-related genes and MMPs were regulated by SLIM-independent pathway. Our present results suggest that the aberrant accumulation of STAT1 protein induced by loss of PKR regulate osteoblast differentiation through both SLIM/STAT1-dependent and -independent pathways.

Original languageEnglish
Pages (from-to)2105-2114
Number of pages10
JournalExperimental Cell Research
Volume315
Issue number12
DOIs
Publication statusPublished - Jul 15 2009
Externally publishedYes

Fingerprint

STAT1 Transcription Factor
Osteoblasts
eIF-2 Kinase
Interleukin-6
Integrin-Binding Sialoprotein
Matrix Metalloproteinase 8
Matrix Metalloproteinase 13
Bone and Bones
Osteopontin
Double-Stranded RNA
Ubiquitination
Post Translational Protein Processing
Collagen Type I
RNA Interference
Matrix Metalloproteinases
Genes
Antiviral Agents
Alkaline Phosphatase
Cell Differentiation
Carcinogenesis

Keywords

  • Differentiation
  • Osteoblast
  • PKR
  • SLIM
  • STAT1

ASJC Scopus subject areas

  • Cell Biology

Cite this

PKR-mediated degradation of STAT1 regulates osteoblast differentiation. / Yoshida, Kaya; Okamura, Hirohiko; Amorim, Bruna Rabelo; Hinode, Daisuke; Yoshida, Hideo; Haneji, Tatsuji.

In: Experimental Cell Research, Vol. 315, No. 12, 15.07.2009, p. 2105-2114.

Research output: Contribution to journalArticle

Yoshida, K, Okamura, H, Amorim, BR, Hinode, D, Yoshida, H & Haneji, T 2009, 'PKR-mediated degradation of STAT1 regulates osteoblast differentiation', Experimental Cell Research, vol. 315, no. 12, pp. 2105-2114. https://doi.org/10.1016/j.yexcr.2009.02.003
Yoshida, Kaya ; Okamura, Hirohiko ; Amorim, Bruna Rabelo ; Hinode, Daisuke ; Yoshida, Hideo ; Haneji, Tatsuji. / PKR-mediated degradation of STAT1 regulates osteoblast differentiation. In: Experimental Cell Research. 2009 ; Vol. 315, No. 12. pp. 2105-2114.
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