Advances in CANCER RESEARCH Volume 74 This Page Intentionally Left Blank Advances in CANCER RESEARCH Volume 74 Edited by George F. Vande Woude ABL-Basic Research Program National Cancer Institute Frederick Cancer Research and Development Center Frederick, Maryland George Klein Microbiology and Tumor Biology Center Karolinska lnstitutet Stockholm, Sweden ACADEMIC PRESS San Diego London Boston New York Sydney Tokyo Toronto This book is printed on acid-free paper. @ Copyright 0 1998 by ACADEMIC PRESS All Rights Reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the Publisher. The appearance of the code at the bottom of the first page of a chapter in this book indicates the Publisher’s consent that copies of the chapter may be made for personal or internal use of specific clients. This consent is given on the condition, however, that the copier pay the stated per copy fee through the Copyright Clearance Center. Inc. (222 Rosewood Drive, Danvers, Massachusetts 0 1923). for copying beyond that permitted by Sections 107 or 108 of the U.S. Copyright Law. This consent does not extend to other kinds of copying, such as copying for general distribution, for advertising or promotional purposes, for creating new collective works, or for resale. Copy fees for pre-1998 chapters are as shown on the title pages. If no fee code appears on the title page, the copy fee is the same as for current chapters. 0065-230>(/98 $25.00 Academic Press a division of Harcourt Brace & Company 525 B Street, Suite 1900, San Diego, California 92101-4495, USA http://www.apnet.com Academic Press Limited 24-28 Oval Road, London NW I 7DX. UK http://www .hbuk.co.uk/ap/ International Standard Book Number: 0- 12-006674-2 PRINTED IN THE UNITED STATES OF AMERICA 98 9900 01 02 03BB 9 8 7 6 5 4 3 2 I Contents Contributors to Volume 74 vii Key Effectors of Signal Transduction and GI Progression Martine F. Roussel I. Introduction 1 11. The G1 Phase of the Mammalian Cell Cycle 3 111. Signal Transduction and G1 Progression 5 IV. The RAS/ERK Pathway and the Cell Cycle 5 V. V1. VII. VIII. IX. RAS, D-Type Cyclins, and RB Connections 9 Cycling with MYC 11 Interplay between MYC and Cyclin D1 13 Signaling and Cell Cycle Roles of the SRC Family of Kinases 14 Concluding Remarks 15 References 16 p53 in Tumor Progression: Life, Death, and Everything Michael R. A. Mowat I. Introduction 25 11. Biochemical Activities of p53 26 111. p53 and Cell Cycle Control 27 IV. p53 and Apoptosis 29 V. p53 and Tumor Progression 37 References 42 Signal Transduction through MAP Kinase Cascades Timothy S. Lewis, Paul S. Shapiro, and Natalie G. Ahn I. The MAP Kinase (MAPK) Module 49 50 11. Mammalian MAPK Pathways V vi <