Tripartite structure of the avian erythroblastosis virus E26 transforming gene

Abstract

Only two avian oncogenic viruses specifically cause acute leukaemias yet do not transform chicken fibroblasts in culture: E26, which causes erythroblastosis and a low level of concomitant myeloblastosis in chickens, and avian myeloblastosis virus (AMV), which causes myeloblastosis exclusively. Both viruses are replication-defective and share a sequence termed myb (also known as amv) which is unrelated to essential virion genes and is therefore thought to be part of the transforming onc genes of these viruses. However, the genetic structure of the two viruses differs. E26 has a genomic RNA of 5.7 kilobases (kb) and encodes a 135,000 molecular weight gag-related protein (p135) with probable transforming function. We show here by in vitro translation that the 5.7-kb E26 RNA directs the synthesis of p135. Oligonucleotide analysis indicates that E26 RNA contains an internal 0.8-kb subset of the 1.2-kb AMV-related sequence (mybA), termed mybE. A 2.46-kb molecular clone prepared from cDNA transcribed in vitro from E26 RNA contained an E26 transformation-specific (ets) sequence flanked by mybE and an env-related sequence. A complete DNA sequence of this clone indicates that the 1.5-kb ets sequence extends the open reading frame of mybE for 491 amino acids. Thus, the p135 gene of E26 is a genetic hybrid of three distinct elements, approximately 1.2 kb derived from the 5' region of the retroviral gag gene, mybE and the ets sequence, linked in the order 5'-delta gag-mybE-ets-3'. The myeloid leukaemogenicity shared by E26 and AMV correlates with the common myb sequence, while the distinct erythroid leukaemogenicity of E26 correlates with ets and the E26-specific linkage of myb to delta gag.

Epithelium-specific ets transcription factor 2 upregulates cytokeratin 18 expression in pulmonary epithelial cells through an interaction with cytokeratin 18 intron 1

“…V-ets, the first member of the Ets (E26 transformation-specific) transcription factor family, was discovered in 1984 in the avian virus E26 [1]. Since then, more than 30 Ets family members have been identified [2,3].…”

Molecular phylogeny of the ETS gene family

“…Numerous oncogenic versions of some ets family members have been described such as v-ets, the founder of the family which is one of the oncogene of the E26 leukemogenic virus (Leprince et al, 1983;Nunn et al, 1983). Other examples include the erg,¯i-1, FEV, ETV1 and PEA3 genes which are translocated in human myeloid leukemia and in Ewing's sarcoma (Delattre et al, 1992;Shimizu et al, 1993;Zucman et al, 1993;Jeon et al, 1995;Urano et al, 1996;Peter et al, 1997).…”

Erg proteins, transcription factors of the Ets family, form homo, heterodimers and ternary complexes via two distinct domains

“…The proto-oncogene c-ets1 is the cellular progenitor of the v-ets oncogene of the avian leukemia virus E26 and the founder member of the burgeoning ets family (Leprince et al, 1983;Nunn et al, 1983). The common feature of all Ets proteins is their DNA-binding domain (85 amino acid residues), named ETS domain and structured as a winged helix ± turn ± helix motif (Donaldson et al, 1994(Donaldson et al, , 1996Liang et al, 1994;Kodandapani et al, 1996).…”