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Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm

RUNX3 is a transcription factor that functions as a tumor suppressor. In some cancers, RUNX3 expression is down-regulated, usually due to promoter hypermethylation. Recently, it was found that RUNX3 can also be inactivated by the mislocalization of the protein in the cytoplasm. The molecular mechani...

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Autores principales: Goh, Yun-Mi, Cinghu, Senthilkumar, Hong, Eileen Tan Hwee, Lee, You-Soub, Kim, Jang-Hyun, Jang, Ju-Won, Li, Ying-Hui, Chi, Xin-Zi, Lee, Kyeong-Sook, Wee, Heejun, Ito, Yoshiaki, Oh, Byung-Chul, Bae, Suk-Chul
Formato: Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843174/
https://www.ncbi.nlm.nih.gov/pubmed/20100835
http://dx.doi.org/10.1074/jbc.M109.071381
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author Goh, Yun-Mi
Cinghu, Senthilkumar
Hong, Eileen Tan Hwee
Lee, You-Soub
Kim, Jang-Hyun
Jang, Ju-Won
Li, Ying-Hui
Chi, Xin-Zi
Lee, Kyeong-Sook
Wee, Heejun
Ito, Yoshiaki
Oh, Byung-Chul
Bae, Suk-Chul
author_facet Goh, Yun-Mi
Cinghu, Senthilkumar
Hong, Eileen Tan Hwee
Lee, You-Soub
Kim, Jang-Hyun
Jang, Ju-Won
Li, Ying-Hui
Chi, Xin-Zi
Lee, Kyeong-Sook
Wee, Heejun
Ito, Yoshiaki
Oh, Byung-Chul
Bae, Suk-Chul
author_sort Goh, Yun-Mi
collection PubMed
description RUNX3 is a transcription factor that functions as a tumor suppressor. In some cancers, RUNX3 expression is down-regulated, usually due to promoter hypermethylation. Recently, it was found that RUNX3 can also be inactivated by the mislocalization of the protein in the cytoplasm. The molecular mechanisms controlling this mislocalization are poorly understood. In this study, we found that the overexpression of Src results in the tyrosine phosphorylation and cytoplasmic localization of RUNX3. We also found that the tyrosine residues of endogenous RUNX3 are phosphorylated and that the protein is localized in the cytoplasm in Src-activated cancer cell lines. We further showed that the knockdown of Src by small interfering RNA, or the inhibition of Src kinase activity by a chemical inhibitor, causes the re-localization of RUNX3 to the nucleus. Collectively, our results demonstrate that the tyrosine phosphorylation of RUNX3 by activated Src is associated with the cytoplasmic localization of RUNX3 in gastric and breast cancers.
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spelling pubmed-28431742010-04-02 Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm Goh, Yun-Mi Cinghu, Senthilkumar Hong, Eileen Tan Hwee Lee, You-Soub Kim, Jang-Hyun Jang, Ju-Won Li, Ying-Hui Chi, Xin-Zi Lee, Kyeong-Sook Wee, Heejun Ito, Yoshiaki Oh, Byung-Chul Bae, Suk-Chul J Biol Chem Molecular Bases of Disease RUNX3 is a transcription factor that functions as a tumor suppressor. In some cancers, RUNX3 expression is down-regulated, usually due to promoter hypermethylation. Recently, it was found that RUNX3 can also be inactivated by the mislocalization of the protein in the cytoplasm. The molecular mechanisms controlling this mislocalization are poorly understood. In this study, we found that the overexpression of Src results in the tyrosine phosphorylation and cytoplasmic localization of RUNX3. We also found that the tyrosine residues of endogenous RUNX3 are phosphorylated and that the protein is localized in the cytoplasm in Src-activated cancer cell lines. We further showed that the knockdown of Src by small interfering RNA, or the inhibition of Src kinase activity by a chemical inhibitor, causes the re-localization of RUNX3 to the nucleus. Collectively, our results demonstrate that the tyrosine phosphorylation of RUNX3 by activated Src is associated with the cytoplasmic localization of RUNX3 in gastric and breast cancers. American Society for Biochemistry and Molecular Biology 2010-03-26 2010-01-25 /pmc/articles/PMC2843174/ /pubmed/20100835 http://dx.doi.org/10.1074/jbc.M109.071381 Text en © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles
spellingShingle Molecular Bases of Disease
Goh, Yun-Mi
Cinghu, Senthilkumar
Hong, Eileen Tan Hwee
Lee, You-Soub
Kim, Jang-Hyun
Jang, Ju-Won
Li, Ying-Hui
Chi, Xin-Zi
Lee, Kyeong-Sook
Wee, Heejun
Ito, Yoshiaki
Oh, Byung-Chul
Bae, Suk-Chul
Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm
title Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm
title_full Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm
title_fullStr Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm
title_full_unstemmed Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm
title_short Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm
title_sort src kinase phosphorylates runx3 at tyrosine residues and localizes the protein in the cytoplasm
topic Molecular Bases of Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843174/
https://www.ncbi.nlm.nih.gov/pubmed/20100835
http://dx.doi.org/10.1074/jbc.M109.071381
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