The various domains of v-myb and v-ets oncogenes of E26 retrovirus contribute differently, but cooperatively, in transformation of hematopoietic lineages.
The genome of the avian leukemia virus E26 is a unique example of association between two transcription factors which appear as a fused composite nuclear oncoprotein, P135gag-myb-ets. Previous studies with E26 have shown that v-myb and v-ets must cooperate to fully transform both erythrocytic and myelomonocytic precursor cells in vivo and in vitro. To analyse further the contribution of the individual domains involved in the transformation of various hematopoietic lineages, we have constructed several mutant viruses expressing a fusion protein with deletions in either v-myb or v-ets. We show here that integrity of the v-ets oncogene is necessary for transformation of the erythrocytic cells but that neither the DNA-binding domain nor the trans-activating domain of v-myb is required for this transformation. The DNA-binding domain of v-ets is necessary to transform myelomonocytic cells. Furthermore, we show that E26 onco-protein also transforms granulocytic cells. The v-ets DNA-binding domain is not necessary to transform them, whereas deleting the v-myb DNA-binding domain strongly reduces transformation of these cells. These data show that the v-myb and v-ets DNA-binding domains provide quite different contributions to the transformation of various hematopoietic lineages by E26.
Domenget
C
C
Laboratoire de Biologie Moléculaire et Cellulaire, UMR 13 CNRS, Ecole Normale Supérieure de Lyon, France.
Leprince
D
D
Pain
B
B
Peyrol
S
S
Li
R P
RP
Stehelin
D
D
Samarut
J
J
Jurdic
P
P
D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D001483:Base Sequence; D001854:Bone Marrow Cells; D002471:Cell Transformation, Neoplastic; D002645:Chickens; D017353:Gene Deletion; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D008969:Molecular Sequence Data; D020626:Oncogene Proteins v-myb; D009857:Oncogenes; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*
D020626:Oncogene Proteins v-myb; D015682:Retroviridae Proteins, Oncogenic; C050379:oncogene proteins v-ets