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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Casein kinase 2 promotes the TGF-β-induced activation of α-tubulin acetyltransferase 1 in fibroblasts cultured on a soft matrix

  • You, Eunae (Department of Life Science, Chung-Ang University) ;
  • Jeong, Jangho (Department of Life Science, Chung-Ang University) ;
  • Lee, Jieun (Department of Life Science, Chung-Ang University) ;
  • Keum, Seula (Department of Life Science, Chung-Ang University) ;
  • Hwang, Ye Eun (Department of Life Science, Chung-Ang University) ;
  • Choi, Jee-Hye (Department of Life Science, Chung-Ang University) ;
  • Rhee, Sangmyung (Department of Life Science, Chung-Ang University)
  • Received : 2022.01.30
  • Accepted : 2022.03.02
  • Published : 2022.04.30
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Abstract

Cell signals for growth factors depend on the mechanical properties of the extracellular matrix (ECM) surrounding the cells. Microtubule acetylation is involved in the transforming growth factor (TGF)-β-induced myofibroblast differentiation in the soft ECM. However, the mechanism of activation of α-tubulin acetyltransferase 1 (α-TAT1), a major α-tubulin acetyltransferase, in the soft ECM is not well defined. Here, we found that casein kinase 2 (CK2) is required for the TGF-β-induced activation of α-TAT1 that promotes microtubule acetylation in the soft matrix. Genetic mutation and pharmacological inhibition of CK2 catalytic activity specifically reduced microtubule acetylation in the cells cultured on a soft matrix rather than those cultured on a stiff matrix. Immunoprecipitation analysis showed that CK2α, a catalytic subunit of CK2, directly bound to the C-terminal domain of α-TAT1, and this interaction was more prominent in the cells cultured on the soft matrix. Moreover, the substitution of alanine with serine, the 236th amino acid located at the C-terminus, which contains the CK2-binding site of α-TAT1, significantly abrogated the TGF-β-induced microtubule acetylation in the soft matrix, indicating that the successful binding of CK2 and the C-terminus of α-TAT1 led to the phosphorylation of serine at the 236th position of amino acids in α-TAT1 and regulation of its catalytic activity. Taken together, our findings provide novel insights into the molecular mechanisms underlying the TGF-β-induced activation of α-TAT1 in a soft matrix.

Keywords

Acknowledgement

This research was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT) (NRF-2020R1A2C2007389) and the Chung-Ang University Research Grant (2020).

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