Siah-family proteins in lung cancer

Institution:	The Burnham Institute for Medical Research
Investigator(s):	Shu-ichi Matsuzawa, Ph.D.
Award Cycle:	2000 (Cycle 9)	Grant #: 9FT-0183	Award: $74,560
Subject Area:	Cancer
Award Type:	Postdoctoral Fellowship Awards

Abstracts

Initial Award Abstract

Defects in the control of cell division occur in essentially all cancers, including those that arise in the lung. The molecular events that underlie the aberrant growth of malignant cells are only partially understood. With each new insight into the mechanisms responsible for tumor growth, scientists are provided with additional molecular targets for potential therapeutic intervention. In this proposal, we seek to understand the mechanisms of an intracellular cell growth regulator, called Siah. We have determined that Siah inhibits cancer cell growth and that it can be induced by some stimuli that cause arrest of tumor cell division. To understand how Siah functions, we cloned genes encoding proteins that bind to Siah. By studying the interactions of Siah with these other proteins, we hope to gain novel insights into aberrant growth regulation in lung cancers and to devise strategies for new therapeutic approaches to cancer. Moreover, some of the proteins targeted by Siah are relevant to attempts to prevent cancres of the lung using vitamin-A-like drugs (retinoids), suggesting that information derived from our studies could suggest novel strategies for cancer prevention in persons who refused to abandon cigarette smoking. Our goals are to define some of the mechanisms which Siah-family proteins use to control the turnover of various target proteins involved in cell growth regulation, and to understand more about the regulation of Siah-family gene expression in lung cancers.

Publications

Siah-1 and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses
Periodical: Molecular and Cellular Biochemistry			Index Medicus:
Authors: Matsuzawa S, Reed JC				ART
Yr: 2001	Vol: 7	Nbr:	Abs:	Pg: 915-926

TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-a induced apoptosis
Periodical: Journal of Biological Chemistry			Index Medicus:
Authors: Leo E, Deveraux Q, Buchholtz C, et al				ART
Yr: 2001	Vol: 276	Nbr:	Abs:	Pg: 8087-8093

Human tastinm, a proline-rich cytoplasmic protein, associates with the microtubular cytoskeleton.
Periodical: Biochemical Journal			Index Medicus:
Authors: Nadano D, Nakayama J, Matsuzawa S, Sato T, Matsuda T, and Fukuda NM				ART
Yr: 2002	Vol: 364	Nbr:	Abs:	Pg: 669 - 677

TUCAN: An anti-apoptotic CARD family protein over-expressed in cancer.
Periodical: Journal of Biological Chemistry			Index Medicus:
Authors: Pathan N, Marusawa H, Krajewska M, Matsuzawa S, Kim H, Okada K, Torii S, et al.				ART
Yr: 2001	Vol: 276	Nbr:	Abs:	Pg: 32220 - 32229

Siah-1 and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses
Periodical: Molecular and Cellular Biochemistry			Index Medicus:
Authors: Matsuzawa S, Reed JC				ART
Yr: 2001	Vol: 7	Nbr:	Abs:	Pg: 915-926

TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-a induced apoptosis
Periodical: Journal of Biological Chemistry			Index Medicus:
Authors: Leo E, Deveraux Q, Buchholtz C, et al				ART
Yr: 2001	Vol: 276	Nbr:	Abs:	Pg: 8087-8093

Human tastinm, a proline-rich cytoplasmic protein, associates with the microtubular cytoskeleton.
Periodical: Biochemical Journal			Index Medicus:
Authors: Nadano D, Nakayama J, Matsuzawa S, Sato T, Matsuda T, and Fukuda NM				ART
Yr: 2002	Vol: 364	Nbr:	Abs:	Pg: 669 - 677

TUCAN: An anti-apoptotic CARD family protein over-expressed in cancer.
Periodical: Journal of Biological Chemistry			Index Medicus:
Authors: Pathan N, Marusawa H, Krajewska M, Matsuzawa S, Kim H, Okada K, Torii S, et al.				ART
Yr: 2001	Vol: 276	Nbr:	Abs:	Pg: 32220 - 32229