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.

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.

journal_name

Oncogene

journal_title

Oncogene

authors

Sutherland BW,Kucab J,Wu J,Lee C,Cheang MC,Yorida E,Turbin D,Dedhar S,Nelson C,Pollak M,Leighton Grimes H,Miller K,Badve S,Huntsman D,Blake-Gilks C,Chen M,Pallen CJ,Dunn SE

doi

10.1038/sj.onc.1208590

subject

Has Abstract

pub_date

2005-06-16 00:00:00

pages

4281-92

issue

26

eissn

0950-9232

issn

1476-5594

pii

1208590

journal_volume

24

pub_type

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