Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells

Brent W. Sutherland, Jill Kucab, Joyce Wu, Cathy Lee, Maggie C U Cheang, Erika Yorida, Dmitry Turbin, Shoukat Dedhar, Colleen Nelson, Michael Pollak, H. Leighton Grimes, Kathy Miller, Sunil Badve, David Huntsman, C. Blake-Gilks, Min Chen, Catherine J. Pallen, Sandra E. Dunn

Research output: Contribution to journalArticle

188 Citations (Scopus)

Abstract

Akt/PKB is a serine/threonine kinase that promotes tumor cell growth by phosphorylating transcription factors and cell cycle proteins. There is particular interest in finding tumor-specific substrates for Akt to understand how this protein functions in cancer and to provide new avenues for therapeutic targeting. Our laboratory sought to identify novel Akt substrates that are expressed in breast cancer. In this study, we determined that activated Akt is positively correlated with the protein expression of the transcription/ translation factor Y-box binding protein-1 (YB-1) in primary breast cancer by screening tumor tissue microarrays. We therefore questioned whether Akt and YB-1 might be functionally linked. Herein, we illustrate that activated Akt binds to and phosphorylates the YB-1 cold shock domain at Ser102. We then addressed the functional significance of disrupting Ser102 by mutating it to Ala102. Following the stable expression of Flag:YB-1 and Flag:YB-1 (Ala102) in MCF-7 cells, we observed that disruption of the Akt phosphorylation site on YB-1 suppressed tumor cell growth in soft agar and in monolayer. This correlated with an inhibition of nuclear translocation by the YB-1(Ala102) mutant. In conclusion, YB-1 is a new Akt substrate and disruption of this specific site inhibits tumor cell growth.

Original languageEnglish
Pages (from-to)4281-4292
Number of pages12
JournalOncogene
Volume24
Issue number26
DOIs
StatePublished - Jun 16 2005

Fingerprint

Y-Box-Binding Protein 1
Shock
Breast Neoplasms
Growth
Neoplasms
Transcription Factors
Cell Cycle Proteins
Protein-Serine-Threonine Kinases
MCF-7 Cells
Early Detection of Cancer
Agar
Proteins
Phosphorylation

Keywords

  • Akt
  • Breast cancer
  • Cold shock domain
  • Phosphorylation
  • Signal transduction
  • YB-1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells. / Sutherland, Brent W.; Kucab, Jill; Wu, Joyce; Lee, Cathy; Cheang, Maggie C U; Yorida, Erika; Turbin, Dmitry; Dedhar, Shoukat; Nelson, Colleen; Pollak, Michael; Grimes, H. Leighton; Miller, Kathy; Badve, Sunil; Huntsman, David; Blake-Gilks, C.; Chen, Min; Pallen, Catherine J.; Dunn, Sandra E.

In: Oncogene, Vol. 24, No. 26, 16.06.2005, p. 4281-4292.

Research output: Contribution to journalArticle

Sutherland, BW, Kucab, J, Wu, J, Lee, C, Cheang, MCU, Yorida, E, Turbin, D, Dedhar, S, Nelson, C, Pollak, M, Grimes, HL, Miller, K, Badve, S, Huntsman, D, Blake-Gilks, C, Chen, M, Pallen, CJ & Dunn, SE 2005, 'Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells', Oncogene, vol. 24, no. 26, pp. 4281-4292. https://doi.org/10.1038/sj.onc.1208590
Sutherland, Brent W. ; Kucab, Jill ; Wu, Joyce ; Lee, Cathy ; Cheang, Maggie C U ; Yorida, Erika ; Turbin, Dmitry ; Dedhar, Shoukat ; Nelson, Colleen ; Pollak, Michael ; Grimes, H. Leighton ; Miller, Kathy ; Badve, Sunil ; Huntsman, David ; Blake-Gilks, C. ; Chen, Min ; Pallen, Catherine J. ; Dunn, Sandra E. / Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells. In: Oncogene. 2005 ; Vol. 24, No. 26. pp. 4281-4292.
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AU - Wu, Joyce

AU - Lee, Cathy

AU - Cheang, Maggie C U

AU - Yorida, Erika

AU - Turbin, Dmitry

AU - Dedhar, Shoukat

AU - Nelson, Colleen

AU - Pollak, Michael

AU - Grimes, H. Leighton

AU - Miller, Kathy

AU - Badve, Sunil

AU - Huntsman, David

AU - Blake-Gilks, C.

AU - Chen, Min

AU - Pallen, Catherine J.

AU - Dunn, Sandra E.

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N2 - Akt/PKB is a serine/threonine kinase that promotes tumor cell growth by phosphorylating transcription factors and cell cycle proteins. There is particular interest in finding tumor-specific substrates for Akt to understand how this protein functions in cancer and to provide new avenues for therapeutic targeting. Our laboratory sought to identify novel Akt substrates that are expressed in breast cancer. In this study, we determined that activated Akt is positively correlated with the protein expression of the transcription/ translation factor Y-box binding protein-1 (YB-1) in primary breast cancer by screening tumor tissue microarrays. We therefore questioned whether Akt and YB-1 might be functionally linked. Herein, we illustrate that activated Akt binds to and phosphorylates the YB-1 cold shock domain at Ser102. We then addressed the functional significance of disrupting Ser102 by mutating it to Ala102. Following the stable expression of Flag:YB-1 and Flag:YB-1 (Ala102) in MCF-7 cells, we observed that disruption of the Akt phosphorylation site on YB-1 suppressed tumor cell growth in soft agar and in monolayer. This correlated with an inhibition of nuclear translocation by the YB-1(Ala102) mutant. In conclusion, YB-1 is a new Akt substrate and disruption of this specific site inhibits tumor cell growth.

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