title: Src kinase phosphorylates RUNX3 at tyrosine residues and localizes the protein in the cytoplasm.
abstract: 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.
authors.affiliation: Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju 361-763, South Korea.
authors.forename: Yun-Mi
authors.initials: YM
authors.lastname: Goh
authors.affiliation: Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju 361-763, South Korea.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Cinghu
authors.affiliation: Cancer Science Institute Singapore, National University of Singapore and Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
authors.forename: Eileen Tan Hwee
authors.initials: ETH
authors.lastname: Hong
authors.affiliation: Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju 361-763, South Korea.
authors.forename: You-Soub
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju 361-763, South Korea.
authors.forename: Jang-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju 361-763, South Korea.
authors.forename: Ju-Won
authors.initials: JW
authors.lastname: Jang
authors.affiliation: Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju 361-763, South Korea.
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju 361-763, South Korea.
authors.forename: Xin-Zi
authors.initials: XZ
authors.lastname: Chi
authors.affiliation: Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju 361-763, South Korea.
authors.forename: Kyeong-Sook
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju 361-763, South Korea.
authors.forename: Heejun
authors.initials: H
authors.lastname: Wee
authors.affiliation: Cancer Science Institute Singapore, National University of Singapore and Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-ku, Inchon 406-840, South Korea. Electronic address: bcoh@gachon.ac.kr.
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Oh
authors.affiliation: Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju 361-763, South Korea. Electronic address: scbae@chungbuk.ac.kr.
authors.forename: Suk-Chul
authors.initials: SC
authors.lastname: Bae
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D034741:RNA, Small Interfering; C493729:Runx3 protein, human; D014443:Tyrosine; D019061:src-Family Kinases