Isolation and cloning of JTAP-1: a cathepsin like gene upregulated in response to V-Jun induced cell transformation.
The oncogenic potential of Jun in chicken embryo fibroblasts (CEF) varies depending on its structure. V-Jun, which has a number of structural differences from c-Jun is highly transforming and tumorigenic. C-Jun however, is only weakly transforming and is not tumorigenic. We have used this difference in oncogenic potential between v-Jun and c-Jun to screen for downstream target genes associated with the v-Jun induced transformed phenotype. We describe here the identification, cloning and characterization of one of these genes, JTAP-1. JTAP-1 is consistently overexpressed 7 to 10-fold in CEF transformed by v-Jun compared with c-Jun overexpressing or normal CEF. This pattern of expression suggests that JTAP-1 is associated with the transformed phenotype. DNA and amino acid homology search analysis revealed that JTAP-1 shares a high degree of similarity with over 100 cysteine proteases from a variety of species and is likely the chicken homolog of cathepsin O. Analysis of expression of JTAP-1 in CEF overexpressing other oncogenes including v-Ha-ras, v-Src, c-Fos, and Myc revealed that it's overexpression is unique to v-Jun transformed cells. Thus, JTAP-1 is likely a specific target of v-Jun overexpression and not simply a consequence of cell transformation.
Hadman
M
M
Department of Microbiology and Immunology, Eastern Virginia Medical School, Norfolk, VA 23501, USA.
Gabos
L
L
Loo
M
M
Sehgal
A
A
Bos
T J
TJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D002645:Chickens; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000235:genetics*; D010450:Endopeptidases; D005786:Gene Expression Regulation; D016758:Genes, jun; D006801:Humans; D008969:Molecular Sequence Data; D011817:Rabbits; D015854:Up-Regulation
D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534130:CTSK protein, human; D056657:Cathepsin K; C534179:CTSO protein, human