An oncogenic fusion product of the phosphatidylinositol 3-kinase p85beta subunit and HUMORF8, a putative deubiquitinating enzyme.
Peripheral blood cell DNA from a patient with a chronic myeloproliferative disorder was tested in the tumorigenicity assay. Upon tumor induction in nude mice we isolated a human oncogene by means of genomic cloning, exon trap analysis and cDNA cloning. Sequence analysis revealed a fusion product of the p85beta subunit of phosphatidylinositol (PI) 3-kinase and HUMORF8, a putative deubiquitinating enzyme, which has been generated during the DNA transfection process. Application of the tumorigenicity assay to various p85beta and HUMORF8 cDNA constructs indicated that the recombination of both genes rather than the truncation of one of the fusion partners renders the chimeric protein tumorigenic. Moreover, sequence analysis of human wildtype p85beta revealed an alanine for serine substitution at a site important for the regulation of the lipid kinase activity of PI 3-kinase in human p85alpha. This variation may relate to differences in the mode of signal transduction from both p85 isoforms.
Janssen
J W
JW
Institut für Humangenetik, Ruprecht-Karls-Universität Heidelberg, Germany.
Schleithoff
L
L
Bartram
C R
CR
Schulz
A S
AS
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D015197:Carcinogenicity Tests; D018076:DNA, Complementary; D010450:Endopeptidases / Q000235:genetics*; D056827:Endosomal Sorting Complexes Required for Transport; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009196:Myeloproliferative Disorders / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D043222:Ubiquitin Thiolesterase
D018076:DNA, Complementary; D056827:Endosomal Sorting Complexes Required for Transport; D015513:Oncogene Proteins; D011993:Recombinant Fusion Proteins; D019869:Phosphatidylinositol 3-Kinases; D010450:Endopeptidases; C541534:USP8 protein, human; D043222:Ubiquitin Thiolesterase; C091939:ubiquitin isopeptidase