Rem-1, a putative direct target gene of the Myb-Ets fusion oncoprotein in haematopoietic progenitors, is a member of the recoverin family.
The Myb-Ets oncoprotein encoded by the E26 avian leukaemia virus represents a fusion of two transcription factors which cooperate in transforming multipotent haematopoietic progenitors (MEPs) in vitro and in vivo. Previous studies with a temperature sensitive mutant in ets (ts1.1 E26) have suggested that the Ets part of the Myb-Ets fusion protein blocks multilineage differentiation of transformed MEPs, by regulating specific target genes. Using this system in a differential screening approach we have now identified a new gene, called rem-1, as a target for the E26 virus. Following shift of ts1.1 mutant transformed cells to the nonpermissive temperature a decreased expression of rem-1 was observed which increased upon downshift. The finding that this reexpression did not require new protein synthesis suggests that the Ets component of the fusion protein directly regulates rem-1 transcription. Rem-1 is related to a family of EF-hand-containing calcium-binding proteins that are predominantly expressed in the brain and in retinal cells. This family includes recoverin and visinin, proteins that have been implicated in regulating photoreception. Rem-1 is likewise expressed in these tissues but in addition in haematopoietic cells and in the gut. Enforced expression of rem-1 in ts1.1-transformed MEP cells, using a retroviral vector, showed that this gene is not sufficient to block their differentiation, but that it may provide them with a growth advantage.
Kraut
N
N
Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
Frampton
J
J
Graf
T
T
D000595:Amino Acid Sequence; D000818:Animals; D009189:Avian Myeloblastosis Virus / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002460:Cell Line; D018076:DNA, Complementary; D005136:Eye Proteins; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D051597:Hippocalcin; D008074:Lipoproteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins; D020626:Oncogene Proteins v-myb; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D051603:Recoverin; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D005136:Eye Proteins; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; D020626:Oncogene Proteins v-myb; D015514:Oncogene Proteins, Fusion; C092839:Rem-1 protein, chicken; D015682:Retroviridae Proteins, Oncogenic; C050379:oncogene proteins v-ets; D051603:Recoverin; D051597:Hippocalcin