Chromosomal localization of phospholipase A2 activating protein, an Ets2 target gene, to 9p21.
A murine Ets2 target gene isolated by differential display cloning was identified as the phospholipase A2 activating protein (PLAA) gene. A 2.7-kb human cDNA demonstrating high homology to mouse and rat Plaa genes was then isolated and characterized. Human PLAA contains six WD-40 repeat motifs and three different protein kinase consensus domains. Fluorescence in situ hybridization (FISH) mapping placed PLAA on chromosome 9p21, a region frequently deleted in various cancers. A comprehensive mapping strategy was employed to define further the chromosomal localization of PLAA relative to CDKN2A within the 9p21 locus. Radiation hybrid mapping placed the gene 7.69 cR from WI-5735 (LOD >3.0), a marker in close proximity to CDKN2A and CDKN2B. Yeast artificial chromosome (YAC) mapping localized PLAA proximal to the CDKN2A/CDKN2B genes and to a region flanked by D9S171 and INFA commonly deleted in many neoplasms. Two YACs contained both PLAA and D9S259, a marker present in a second more proximal minimal deleted region observed in cutaneous melanoma and squamous cell lung carcinoma. Double-color fiber FISH mapping confirmed the location of PLAA centromeric to D9S171 and CDKN2A/CDKN2B. The mapping data suggest a possible tumor suppressor role for this gene.
Beatty
B G
BG
Department of Cell and Molecular Biology, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, M5G 1L5, Canada. barbara@beatty5.com
Qi
S
S
Pienkowska
M
M
Herbrick
J A
JA
Scheidl
T
T
Zhang
Z M
ZM
Kola
I
I
Scherer
S W
SW
Seth
A
A
D000818:Animals; D017101:Bacteriophage P1 / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D004268:DNA-Binding Proteins; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D008126:Lod Score; D008175:Lung Neoplasms / Q000235:genetics; D008545:Melanoma / Q000235:genetics; D051379:Mice; D020161:Physical Chromosome Mapping; D011506:Proteins / Q000235:genetics*; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051381:Rats; D012097:Repressor Proteins; D012878:Skin Neoplasms / Q000235:genetics; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494069:ETS2 protein, human; C494070:Ets2 protein, mouse; C494071:Ets2 protein, rat; D011506:Proteins; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C055324:phospholipase A2-activating protein