Synthetic lethality of retinoblastoma mutant cells in the Drosophila eye by mutation of a novel peptidyl prolyl isomerase gene.
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 eliminate Rbf(-) cells, but allow Rbf(+) cells 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.
Edgar
Kyle A
KA
Exelixis, South San Francisco, California 94083, USA.
Belvin
Marcia
M
Parks
Annette L
AL
Whittaker
Kellie
K
Mahoney
Matt B
MB
Nicoll
Monique
M
Park
Christopher C
CC
Winter
Christopher G
CG
Chen
Feng
F
Lickteig
Kim
K
Ahmad
Ferhad
F
Esengil
Hanife
H
Lorenzi
Matthew V
MV
Norton
Amanda
A
Rupnow
Brent A
BA
Shayesteh
Laleh
L
Tabios
Mariano
M
Young
Lynn M
LM
Carroll
Pamela M
PM
Kopczynski
Casey
C
Plowman
Gregory D
GD
Friedman
Lori S
LS
Francis-Lang
Helen L
HL
D000595:Amino Acid Sequence; D000818:Animals; D004331:Drosophila melanogaster / Q000196:embryology* / Q000201:enzymology / Q000235:genetics; D005123:Eye / Q000196:embryology* / Q000201:enzymology; D008969:Molecular Sequence Data; D009154:Mutation; D019696:Peptidylprolyl Isomerase / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics*
D016160:Retinoblastoma Protein; D019696:Peptidylprolyl Isomerase
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