Casein kinase 2 promotes the TGF-モ–induced activation of メ-tubulin acetyltransferase 1 in fibroblasts cultured on a soft matrix |
Eunae You1,# (Research worker), Jangho Jeong1,# (Research worker), Jieun Lee1 (Research worker), Seula Keum1 (Graduate student), Ye Eun Hwang1 (Graduate student), Jee-Hye Choi 1,# (Professor), Sangmyung Rhee 1,*,# (Professor) |
1Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea |
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)-モ–induced myofibroblast differentiation in the soft ECM. However, the mechanism of activation of メ-tubulin acetyltransferase 1 (メ-TAT1), a major メ-tubulin acetyltransferase, in the soft ECM is not well defined. Here, we found that casein kinase 2 (CK2) is required for the TGF-モ–induced activation of メ-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 CK2メ, a catalytic subunit of CK2, directly bound to the C-terminal domain of メ-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 メ-TAT1, significantly abrogated the TGF-モ–induced microtubule acetylation in the soft matrix, indicating that the successful binding of CK2 and the C-terminus of メ-TAT1 led to the phosphorylation of serine at the 236th position of amino acids in メ-TAT1 and regulation of its catalytic activity. Taken together, our findings provide novel insights into the molecular mechanisms underlying the TGF-モ–induced activation of メ-TAT1 in a soft matrix.
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Abstract, Accepted Manuscript(in press) [Submitted on January 30, 2022, Accepted on March 2, 2022] |
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