PMID- 10321731
OWN - NLM
STAT- MEDLINE
DCOM- 19990603
LR  - 20061115
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 12
DP  - 1999 Mar 25
TI  - Mrvi1, a common MRV integration site in BXH2 myeloid leukemias, encodes a protein
      with homology to a lymphoid-restricted membrane protein Jaw1.
PG  - 2069-84
AB  - Ecotropic MuLVs induce myeloid leukemia in BXH2 mice by insertional mutagenesis
      of cellular proto-oncogenes or tumor suppressor genes. Disease genes can thus be 
      identified by viral tagging as common sites of viral integration in BXH2
      leukemias. Previous studies showed that a frequent common integration site in
      BXH2 leukemias is the Nf1 tumor suppressor gene. Unexpectedly, about half of the 
      viral integrations at Nf1 represented a previously undiscovered defective
      nonecotropic virus, termed MRV. Because other common integration sites in BXH2
      leukemias encoding proto-oncogenes contain ecotropic rather than MRV viruses, it 
      has been speculated that MRV viruses may selectively target tumor suppressor
      genes. To determine if this were the case, 21 MRV-positive BXH2 leukemias were
      screened for new MRV common integration sites. One new site, Mrvi1 was identified
      that was disrupted by MRV in two of the leukemias. Ecotropic virus did not
      disrupt Mrvi1 in 205 ecotropic virus-positive leukemias, suggesting that Mrvi1 is
      specifically targeted by MRV. Mrvi1 encodes a novel protein with homology to
      Jaw1, a lymphoid restricted type II membrane protein that localizes to the
      endoplasmic reticulum. MRV integration occurs at the 5' end of the gene between
      two differentially used promoters. Within hematopoietic cells, Mrvi1 expression
      is restricted to megakaryocytes and some myeloid leukemias. Like Jaw1, which is
      down-regulated during lymphoid differentiation, Mrv1 is downregulated during
      monocytic differentiation of BXH2 leukemias. Taken together, these data suggest
      that MRV integration at Mrvi1 induces myeloid leukemia by altering the expression
      of a gene important for myeloid cell growth and/or differentiation. Experiments
      are in progress to test whether Mrvi1 is a tumor suppressor gene.
FAU - Shaughnessy, J D Jr
AU  - Shaughnessy JD Jr
AD  - Division of Hematology and Oncology, Department of Medicine, University of
      Arkansas for Medical Sciences, Little Rock 72205, USA.
FAU - Largaespada, D A
AU  - Largaespada DA
FAU - Tian, E
AU  - Tian E
FAU - Fletcher, C F
AU  - Fletcher CF
FAU - Cho, B C
AU  - Cho BC
FAU - Vyas, P
AU  - Vyas P
FAU - Jenkins, N A
AU  - Jenkins NA
FAU - Copeland, N G
AU  - Copeland NG
LA  - eng
SI  - GENBANK/AF081249
SI  - GENBANK/AF081250
SI  - GENBANK/U63407
SI  - GENBANK/U63408
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (LRMP protein, human)
RN  - 0 (Lrmp protein, mouse)
RN  - 0 (MRVI1 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Mrvi1 protein, mouse)
RN  - 0 (Phosphoproteins)
SB  - IM
MH  - Alternative Splicing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Bone Marrow Cells
MH  - Cell Differentiation
MH  - Chromosome Mapping
MH  - Cloning, Molecular
MH  - Defective Viruses
MH  - Down-Regulation
MH  - Endoplasmic Reticulum
MH  - Humans
MH  - Leukemia, Myeloid/etiology/*genetics/*virology
MH  - Lymphoid Tissue/cytology
MH  - Macrophages/cytology
MH  - Membrane Proteins/*genetics
MH  - Mice
MH  - Molecular Sequence Data
MH  - Monocytes/cytology
MH  - *Mutagenesis, Insertional
MH  - *Phosphoproteins
MH  - Retroviridae/genetics
MH  - Sequence Analysis, DNA
MH  - Sequence Homology, Amino Acid
MH  - Tissue Distribution
MH  - *Virus Integration
EDAT- 1999/05/13 02:05
MHDA- 2001/03/28 10:01
CRDT- 1999/05/13 02:05
PHST- 1999/05/13 02:05 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/05/13 02:05 [entrez]
AID - 10.1038/sj.onc.1202419 [doi]
PST - ppublish
SO  - Oncogene. 1999 Mar 25;18(12):2069-84. doi: 10.1038/sj.onc.1202419.