Genetics. Published Articles Ahead of Print: March 2, 2005, Copyright © 2005
doi:10.1534/genetics.104.036343


A more recent version of this article appeared on May 1, 2005.

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Synthetic lethality of retinoblastoma mutant cells in the Drosophila eye by mutation of a novel peptidyl prolyl isomerase gene

Kyle A. Edgar 1, Marcia Belvin 2*, Annette L. Parks 3, Kellie Whittaker 1, Matt B. Mahoney 4, Monique Nicoll 1, Christopher C. Park 5, Christopher G. Winter 1, Feng Chen 6, Kim Lickteig 7, Ferhad Ahmad 1, Hanife Esengil 8, Matthew V. Lorenzi 9, Amanda Norton 10, Brent A. Rupnow 9, Laleh Shayesteh 1, Mariano Tabios 1, Lynn M. Young 11, Pamela M. Carroll 12, Casey Kopczynski 13, Gregory D. Plowman 14, Lori S. Friedman 14 and Helen L. Francis-Lang 1

1 Exelixis, Inc.
2 Genentech, Inc
3 Boston College
4 EnVivo Pharmaceuticals
5 UCLA
6 DOE Joint Genome Institute
7 Celera Genomics
8 Stanford University
9 Bristol-Myers Squibb Pharmaceutical Research Institute
10 UCSF
11 The Institute for Genomic Research
12 Merck Research Laboratories
13 Biotech Initiative
14 Genentech, Inc.

* To whom correspondence should be addressed. E-mail: marciabelvin{at}yahoo.com.

Submitted on September 15, 2004
Revised on December 20, 2004
Accepted on 25 January 2005


Abstract

Mutations that inactivate the retinoblastoma (Rb) pathway are common in human tumors. Such mutations promote tumor growth by deregulating the G1 cell cycle checkpoint. However, uncontrolled cell cycle progression can also produce new liabilities for cell survival. To uncover such liabilities in Rb mutant cells, we performed a clonal screen in the Drosophila eye to identify second-site mutations that are synthetically lethal in Rbf- cells, but allow Rbf+ calls to survive. Here we report the identification of a mutation in a novel highly conserved peptidyl prolyl isomerase (PPIase) that selectively eliminates Rbf- cells from the Drosophila eye.

Key Words: Drosophila, PPIase, Peptidyl prolyl isomerase, Retinoblastoma, Synthetic lethal