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

• Published in: Oncogene Vol. 24; no. 26; pp. 4281 - 4292
• Main Authors: SUTHERLAND, Brent W, KUCAB, Jill, LEIGHTON GRIMES, H, MILLER, Kathy, BADVE, Sunil, HUNTSMAN, David, BLAKE-GILKS, C, MIN CHEN, PALLEN, Catherine J, DUNN, Sandra E, WU, Joyce, LEE, Cathy, CHEANG, Maggie C. U, YORIDA, Erika, TURBIN, Dmitry, DEDHAR, Shoukat, NELSON, Colleen, POLLAK, Michael
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 16.06.2005; Nature Publishing Group
• Subjects: AKT protein; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; CCAAT-Enhancer-Binding Proteins - metabolism; Cell Adhesion; Cell cycle; Cell growth; Cell physiology; Cell Proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cold; Cold shock proteins; Disease Progression; Female; Fundamental and applied biological sciences. Psychology; Humans; Insulin-like growth factors; Kinases; Laboratories; Medicine; Molecular and cellular biology; NFI Transcription Factors; Nuclear factor I; Nuclear transport; Pediatrics; Phosphorylation; Protein-Serine-Threonine Kinases - pharmacology; Protein-serine/threonine kinase; Proteins; Proto-Oncogene Proteins - pharmacology; Proto-Oncogene Proteins c-akt; Research centers; Signal Transduction; Therapeutic targets; Transcription factors; Transcription Factors - metabolism; Tumors; Womens health; Y-Box-Binding Protein 1; British Columbia Canada; Canada; Indiana; Vancouver British Columbia Canada; United States > US; Shock; Phosphorylation; Protein kinase B; YB-1; Growth; Breast cancer; Malignant tumor; Akt; Carcinogenesis; Mammary gland diseases; Binding protein; Signal transduction; cold shock domain
• DOI: 10.1038/sj.onc.1208590
• ISSN: 0950-9232

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.