PMID- 10523652
OWN - NLM
STAT- MEDLINE
DCOM- 19991124
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 11
DP  - 1999 Nov
TI  - Dual transforming activities of the FUS (TLS)-ERG leukemia fusion protein
      conferred by two N-terminal domains of FUS (TLS).
PG  - 7639-50
AB  - The FUS (TLS)-ERG chimeric protein associated with t(16;21)(p11;q22) acute
      myeloid leukemia is structurally similar to the Ewing's sarcoma chimeric
      transcription factor EWS-ERG. We found that both FUS-ERG and EWS-ERG could induce
      anchorage-independent proliferation of the mouse fibroblast cell line NIH 3T3.
      However, only FUS-ERG was able to inhibit the differentiation into neutrophils of
      a mouse myeloid precursor cell line L-G and induce its granulocyte
      colony-stimulating factor-dependent growth. We constructed several deletion
      mutants of FUS-ERG lacking a part of the N-terminal FUS region. A deletion mutant
      lacking the region between amino acids 1 and 173 (exons 1 to 5) lost the NIH
      3T3-transforming activity but retained the L-G-transforming activity. On the
      other hand, a mutant lacking the region between amino acids 174 and 265 (exons 6 
      and 7) lost the L-G-transforming activity but retained the NIH 3T3-transforming
      activity. These results indicate that the N-terminal region of FUS contains two
      independent functional domains required for the NIH 3T3 and L-G transformation,
      which we named TR1 and TR2, respectively. Although EWS intrinsically possessed
      the TR2 domain, the EWS-ERG construct employed lacked the EWS sequence containing
      this domain. Since the TR2 domain is always found in chimeric proteins identified
      from t(16;21) leukemia patients but not in chimeric proteins from Ewing's sarcoma
      patients, it seems that the TR2 function is required only for the leukemogenic
      potential. In addition, we identified three cellular genes whose expression was
      altered by ectopic expression of FUS-ERG and found that these are regulated in
      either a TR1-dependent or a TR2-dependent manner. These results suggest that
      FUS-ERG may activate two independent oncogenic pathways during the leukemogenic
      process by modulating the expression of two different groups of genes
      simultaneously.
FAU - Ichikawa, H
AU  - Ichikawa H
AD  - Radiobiology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 
      104-0045, Japan. hichikaw@ncc.go.jp
FAU - Shimizu, K
AU  - Shimizu K
FAU - Katsu, R
AU  - Katsu R
FAU - Ohki, M
AU  - Ohki M
LA  - eng
SI  - GENBANK/AB028209
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA Primers)
RN  - 0 (Heterogeneous-Nuclear Ribonucleoproteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA-Binding Protein EWS)
RN  - 0 (RNA-Binding Protein FUS)
RN  - 0 (Ribonucleoproteins)
RN  - 0 (TLS-ERG fusion protein, human)
SB  - IM
MH  - 3T3 Cells
MH  - Acute Disease
MH  - Animals
MH  - Base Sequence
MH  - Cell Transformation, Neoplastic/*genetics
MH  - Chromosomes, Human, Pair 16
MH  - Chromosomes, Human, Pair 21
MH  - DNA Primers
MH  - Exons
MH  - Gene Expression Regulation
MH  - Hematopoietic Stem Cells
MH  - Heterogeneous-Nuclear Ribonucleoproteins
MH  - Humans
MH  - Leukemia, Myeloid/etiology/*genetics
MH  - Mice
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Peptide Fragments/genetics
MH  - RNA-Binding Protein EWS
MH  - RNA-Binding Protein FUS
MH  - Ribonucleoproteins/*genetics
MH  - Translocation, Genetic
PMC - PMC84797
EDAT- 1999/10/19 00:00
MHDA- 1999/10/19 00:01
CRDT- 1999/10/19 00:00
PHST- 1999/10/19 00:00 [pubmed]
PHST- 1999/10/19 00:01 [medline]
PHST- 1999/10/19 00:00 [entrez]
AID - 10.1128/mcb.19.11.7639 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Nov;19(11):7639-50. doi: 10.1128/mcb.19.11.7639.