From: Subject: Researchers uncover new mechanism of tumor suppressor Date: Mon, 22 May 2006 19:36:33 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C67DD7.08673520" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.2869 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C67DD7.08673520 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.eurekalert.org/pub_releases/2006-05/su-ru051906.php Researchers uncover new mechanism of tumor = suppressor

Public = release date:=20 21-May-2006
[ | E-mail Article ]

Contact: Mark Shwartz
mshwartz@stanford.edu
650-72= 3-9296
Stanford = University=20

Researchers uncover new mechanism of tumor = suppressor

Findings to be published in the journal=20 Nature

Researchers from the University of Colorado-Denver and Health = Sciences Center and Stanford University have discovered a molecular = mechanism=20 that explains how cells respond to DNA damage and other acute stresses, = and if=20 disrupted can cause cancer. Their findings, which could lead to new = diagnostic=20 markers and cancer treatments with fewer side effects, will appear in = two=20 reports in the May 21 advanced online version of the journal Nature.=20

The studies, led by Tatiana Kutateladze, PhD, an assistant professor = in the=20 UCDHSC Department of Pharmacology, and Or Gozani, MD, PhD, an assistant=20 professor in the Department of Biological Sciences at Stanford = University,=20 revealed the significance of a novel function of the recently discovered = tumor-suppressive molecule, which is thought to inhibit cancer formation = and=20 growth. These findings highlight a new mechanism to regulate gene = expression=20 programs that allow for appropriate responses to DNA damage in normal = cells.=20 When the process breaks down, such damage and other acute stresses are = thought=20 to lead to cancer.=20

The first study, Molecular mechanism of histone H3K4me3 recognition = by plant=20 homeodomain of ING2, was conducted in Kutateladze's laboratory with the=20 assistance of graduate student Pedro Pe=F1a and research assistant = Foteini=20 Davrazou. Other co-authors include Rui Zhao, PhD, an assistant professor = in the=20 UCDHSC Department of Biochemistry and Molecular Genetics; Or Gozani, = Xiaobing=20 Shi and Kay L. Walter from Stanford University's Department of = Biological=20 Sciences; and Vladislav V. Verkhusha from the Department of Anatomy and=20 Structural Biology at the Albert Einstein College of Medicine in New = York.=20

The paper based on their work describes the structural aspects of the = tumor=20 suppressor action, while functional studies were accomplished by = Gozani's group,=20 and are the subject of the second report that will appear in Nature = titled ING2=20 PHD domain links histone H3 lysine 4 methylation to active gene = repression.=20

"Our findings have established the mechanistic principles by which = the=20 inhibitor of growth 2 tumor suppressor recognizes chromatin and = regulates cell=20 growth, proliferation, stress responses and aging. We hope this = discovery opens=20 up new opportunities to establish novel targets to prevent and treat = cancer,"=20 said Kutateladze, a NARSAD Young Investigator and an American Cancer = Society=20 Research Scholar.=20

Research in Kutateladze's laboratory focuses on molecular mechanisms=20 underlying signaling and regulation by chromatin- and lipid-binding = biomolecules=20 implicated in cancer and other human diseases. She employs high field = Nuclear=20 Magnetic Resonance spectroscopy, X-ray crystallography and other = biochemical and=20 biophysical approaches to elucidate three-dimensional atomic-resolution=20 structures and dynamics of proteins to better understand their = physiological=20 functions and relevance to diseases.=20

###

Funding for the studies was provided by the National Institutes of = Health=20 (NIH), Burroughs Welcome, the American Heart Association and the = University of=20 Colorado Cancer Center.=20

Editor's note: The reports will be available after 11 a.m. (MDT), = Sunday, May=20 21 at http://dx.doi.org/10.1038/= nature04814=20 or http://www.nature.com/.=20

Contact: Deborah M=E9ndez-Wilson (303) 724-1520, Deborah.Mendez-Wilson@uch= sc.edu=20

[ | E-mail Article ]

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