Slug is temporally regulated by cyclin e in cell cycle and controls genome stability

W. L. Wang; H. C. Huang; S. H. Kao; Y. C. Hsu; Y. T. Wang; K. C. Li; Y. J. Chen; S. L. Yu; S. P. Wang; T. H. Hsiao; P. C. Yang; T. M. Hong

doi:10.1038/onc.2014.58

Slug is temporally regulated by cyclin e in cell cycle and controls genome stability

W. L. Wang, H. C. Huang, S. H. Kao, Y. C. Hsu, Y. T. Wang, K. C. Li, Y. J. Chen, S. L. Yu, S. P. Wang, T. H. Hsiao, P. C. Yang, T. M. Hong

Institute of Clinical Medicine

Research output: Contribution to journal › Article › peer-review

30 Citations (Scopus)

Abstract

The transcriptional repressor Slug is best known to control epithelial-mesenchymal transition (EMT) and promote cancer invasion/metastasis. In this study, we demonstrate that Slug is temporally regulated during cell cycle progression. At G1/S transition, cyclin E-cyclin-dependent kinase 2 mediates the phosphorylation of Slug at Ser-54 and Ser-104, resulting in its ubiquitylation and degradation. Non-phosphorylatable Slug is markedly stabilized at G1/S transition compared with wild-type Slug and greatly leads to downregulation of DNA synthesis and checkpoint-related proteins, including TOP1, DNA Ligase IV and Rad17, reduces cell proliferation, delays S-phase progression and contributes to genome instability. Our results indicate that Slug has multifaceted roles in cancer progression by controlling both EMT and genome stability.

Original language	English
Pages (from-to)	1116-1125
Number of pages	10
Journal	Oncogene
Volume	34
Issue number	9
DOIs	https://doi.org/10.1038/onc.2014.58
Publication status	Published - 2015 Feb 26

All Science Journal Classification (ASJC) codes

Molecular Biology
Genetics
Cancer Research

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10.1038/onc.2014.58

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title = "Slug is temporally regulated by cyclin e in cell cycle and controls genome stability",

abstract = "The transcriptional repressor Slug is best known to control epithelial-mesenchymal transition (EMT) and promote cancer invasion/metastasis. In this study, we demonstrate that Slug is temporally regulated during cell cycle progression. At G1/S transition, cyclin E-cyclin-dependent kinase 2 mediates the phosphorylation of Slug at Ser-54 and Ser-104, resulting in its ubiquitylation and degradation. Non-phosphorylatable Slug is markedly stabilized at G1/S transition compared with wild-type Slug and greatly leads to downregulation of DNA synthesis and checkpoint-related proteins, including TOP1, DNA Ligase IV and Rad17, reduces cell proliferation, delays S-phase progression and contributes to genome instability. Our results indicate that Slug has multifaceted roles in cancer progression by controlling both EMT and genome stability.",

author = "Wang, {W. L.} and Huang, {H. C.} and Kao, {S. H.} and Hsu, {Y. C.} and Wang, {Y. T.} and Li, {K. C.} and Chen, {Y. J.} and Yu, {S. L.} and Wang, {S. P.} and Hsiao, {T. H.} and Yang, {P. C.} and Hong, {T. M.}",

note = "Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

year = "2015",

month = feb,

day = "26",

doi = "10.1038/onc.2014.58",

language = "English",

volume = "34",

pages = "1116--1125",

journal = "Oncogene",

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T1 - Slug is temporally regulated by cyclin e in cell cycle and controls genome stability

AU - Wang, W. L.

AU - Huang, H. C.

AU - Kao, S. H.

AU - Hsu, Y. C.

AU - Wang, Y. T.

AU - Li, K. C.

AU - Chen, Y. J.

AU - Yu, S. L.

AU - Wang, S. P.

AU - Hsiao, T. H.

AU - Yang, P. C.

AU - Hong, T. M.

PY - 2015/2/26

Y1 - 2015/2/26

N2 - The transcriptional repressor Slug is best known to control epithelial-mesenchymal transition (EMT) and promote cancer invasion/metastasis. In this study, we demonstrate that Slug is temporally regulated during cell cycle progression. At G1/S transition, cyclin E-cyclin-dependent kinase 2 mediates the phosphorylation of Slug at Ser-54 and Ser-104, resulting in its ubiquitylation and degradation. Non-phosphorylatable Slug is markedly stabilized at G1/S transition compared with wild-type Slug and greatly leads to downregulation of DNA synthesis and checkpoint-related proteins, including TOP1, DNA Ligase IV and Rad17, reduces cell proliferation, delays S-phase progression and contributes to genome instability. Our results indicate that Slug has multifaceted roles in cancer progression by controlling both EMT and genome stability.

AB - The transcriptional repressor Slug is best known to control epithelial-mesenchymal transition (EMT) and promote cancer invasion/metastasis. In this study, we demonstrate that Slug is temporally regulated during cell cycle progression. At G1/S transition, cyclin E-cyclin-dependent kinase 2 mediates the phosphorylation of Slug at Ser-54 and Ser-104, resulting in its ubiquitylation and degradation. Non-phosphorylatable Slug is markedly stabilized at G1/S transition compared with wild-type Slug and greatly leads to downregulation of DNA synthesis and checkpoint-related proteins, including TOP1, DNA Ligase IV and Rad17, reduces cell proliferation, delays S-phase progression and contributes to genome instability. Our results indicate that Slug has multifaceted roles in cancer progression by controlling both EMT and genome stability.

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SN - 0950-9232

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SP - 1116

EP - 1125

JO - Oncogene

JF - Oncogene

IS - 9

ER -

Slug is temporally regulated by cyclin e in cell cycle and controls genome stability

Abstract

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