Regulation and localization of ribosomal protein S6 kinase 1 isoforms

Author: Kim Doyil   Akcakanat Argun   Singh Gopal   Sharma Chandeshwar   Meric-Bernstam Funda  

Publisher: Informa Healthcare

ISSN: 0897-7194

Source: Growth Factors, Vol.27, Iss.1, 2009-02, pp. : 12-21

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Abstract

Ribosomal protein S6 kinase 1 (S6K1), a critical mediator of cell growth, is overexpressed in breast cancer and is associated with poor prognosis. S6K1 has two known isoforms, p85S6K1 and p70S6K1. p85S6K1 is characterized by 23 additional amino acids in the N-terminus of p70S6K1. This is thought to target p85S6K1 to the nucleus, while p70S6K1 is mainly cytoplasmic. We sought to determine the activation, regulation, and function of p70S6K1 and p85S6K1 in breast cancer. We found that most breast cancer cell lines expressed both isoforms. Mitogen-dependent pathways concordantly regulated phosphorylation on T389, S371, and T421/S424. Phosphorylation of both isoforms was inhibited by PI3K/mTOR inhibitors. Mitogen-dependent pathways concordantly regulated the phosphorylation of the two isoforms on T389, S371, and T421/S424. Both isoforms had S6 kinase activity. We also detected a p60 isoform with antibodies to the p70S6K1 C-terminal but not the N-terminal. Further studies on S6K1 isoforms are warranted for therapeutically targeting this pathway.

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