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Functions of IRF-1 and Smad3 interaction in lung cancer

Institution: University of California, San Francisco
Investigator(s): Pierre Lee, Ph.D.
Award Cycle: 2001 (Cycle 10) Grant #: 10FT-0141 Award: $69,750
Subject Area: Cancer
Award Type: Postdoctoral Fellowship Awards
Abstracts

Initial Award Abstract
Transforming growth factor-ß (TGF-ß) is an important protein that regulates cell growth and development in many tissues. It is required for the proper development and functioning of the lungs. In healthy lungs, TGF-ß stops the cells lining the trachea and bronchi from multiplying in an uncontrolled manner. Loss of TGF-ß's function is often associated with the initiation and progression of lung cancers.

The effect of TGF-ß on cell growth is mediated inside the cell via a series of protein mediators. We have previously identified one family of such mediators, called Smads, that regulate the activity of many genes. Mutations in this family of proteins have been associated with numerous types of cancers, including lung cancers. Our previous work has shown that Smads work in cooperation with other proteins within the cell to maintain proper cellular functions. Many of these protein partners are not identified. We recently discovered one of these proteins, named IRF-1, that functions with Smads to regulate the activity of certain growth control genes. Mutations of these growth control genes leading to uncontrolled cell proliferation are frequently detected in lung cancers. We propose to define the mechanism of actions of these proteins and the roles they play in the development of lung cancers.

These studies are relevant to lung cancer as lung cancer cells often escape TGF-ß’s growth inhibition. Understanding the molecular basis for this event will provide very important information on how growth control is achieved and this may advance the development of lung cancer therapy.
Publications

Sumoylation of Smad4, the common Smad mediator of transforming growth factor-beta family signaling.
Periodical: Journal of Biological Chemistry Index Medicus:
Authors: Lee PS, Chang C, Liu D, Derynck R ART
Yr: 2003 Vol: 278 Nbr: 30 Abs: Pg: 27853-63