Control of Cell Size Through Phosphorylation of Upstream Binding Factor 1 by Nuclear Phosphatidylinositol 3-kinase

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2004 Jun 16

PMID 15197263

Citations 34

Authors

Robert Drakas

Xiao Tu

Renato Baserga

Affiliations

Soon will be listed here.

Abstract

The insulin-like growth factor I/insulin receptor substrate 1 axis controls, in a nonredundant way, approximately 50% of cell and body size in animals from Drosophila to mice and in cells in culture. Although other factors may also intervene, cell size is strongly dependent on ribosome biogenesis, which is under the control of RNA polymerase I activity. We have previously shown that insulin receptor substrate 1 (IRS-1) translocates to the nuclei and nucleoli, where it binds to the upstream binding factor (UBF) 1, a regulator of RNA polymerase I activity. Activation of UBF1 requires its phosphorylation. However, IRS-1 is not a kinase, and we searched for an intermediate kinase that can phosphorylate UBF1. We demonstrate here that IRS-1 binds also to the phosphatidylinositol 3-kinase (PI3-K) subunits in nuclear extracts, and that the p110 subunit of PI3-K directly phosphorylates and activates UBF1, an exclusively nucleolar protein. The interaction of IRS-1, PI3-K, and UBF1 in the nucleoli provides one of the mechanisms for the effects of IRS-1 on cell and body size.

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