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Footprinting
722
Fol d bac k D NA
FMS was isolated in 1983 and was localized to chromosome 5. FMS was shown to code for the colony monocytic stimulating factor-1 receptor (CSF1R) (Sherr et al., 1985). It is expressed in monocytes produced by the bone marrow, where it is required for monocytic differentiation and survival of macrophages, and is also expressed in the spleen, liver, brain, and placenta. v-fms exhibits constitutive tyrosine kinase activity in the absence of ligand and transforms cells. The differences between oncogenic v-fms and normal cellular FMS are a number of scattered point mutations and the replacement of 50 amino acids at the C-terminus of the human gene with 11 unrelated amino acids in the viral gene. The effects of FMS are cell type dependent. In NIH3T3 mouse fibroblast cells the sequence responsible for transformation was localized to amino acid 301 in the extracellular domain. Regulatory sequences at position 969, when mutated, enhance transformation mediated by mutations in codon 301. However, in hematopoietic FDCP-1 cells the 969 mutations transform these cells, rendering them anchorage- independent and tumorigenic in nude mice, whereas the 301 mutant construct is not transforming. Cells infected with the 969 mutant construct cannot be saturated with concentrations of CSF-1 observed to saturate the wild-type receptor (McGlynn et al., 1998). Screening myeloid (pre)leukemia patients for these mutations revealed that mutations at codon 969 were more frequent than those at codon 301 (Ridge et al., 1990; Tobal et al., 1990), suggesting that the FMS oncogene may be involved in the pathogenesis of this disease (see Gallagher et al., 1997 and references therein).
References
Gallagher A, Darley RL and Padua R (1997) The molecular basis of myelodysplastic syndromes. Haematologica 82: 191±204. McDonough SK, Larsen S, Brodey RS, Stock ND and Hardy WD, Jr (1971) A transmissible feline fibrosarcoma of viral origin. Cancer Research 31: 953±956. McGlynn H, Baker AH and Padua RA (1998) Biological consequences of a point mutation at codon 969 of the FMS gene. Leukemia Research 22: 365±372. Ridge SA, Worwood M, Oscier D, Jacobs A and Padua RA (1990) FMS mutations in myelodysplasia, leukaemia and normal subjects. Proceedings of the National Academy of Sciences, USA 87: 1377±1380. Sherr CJ, Rettenmier CW, Sacca R et al. (1985) The c-fms protooncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell 41: 665±676. Tobal K, Pagliuca A, Bhatt B et al. (1990) Mutations of the human FMS gene (M-CSF receptor) in myelodysplastic syndromes and acute myeloid leukemia. Leukemia 4: 486±494.
See also: Cancer Susceptibility; Leukemia
Foldback DNA J H Miller Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0467
Single-stranded DNA with sequences that permit it to make stable secondary structures by folding back upon itself and forming hydrogen bonds.
Follicular Lymphoma P G Isaacson Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1572
Follicular lymphoma is a neoplasm of germinal center B cells that recapitulates the histology of reactive B-cell follicles. It is one of the commonest nonHodgkin's lymphomas in Western countries. Follicular lymphoma is characterized by t(14;18)(q32;q21) that leads to overexpression of the apoptosis inhibitory bcl-2 protein. It is clinically indolent but ultimately incurable. See also: Cancer Susceptibility
Footprinting Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1843
Footprinting is a technique used to identify the binding site of, for example, a protein in a nucleic acid sequence by virtue of the protection given by the binding site against nuclease attack. See also: Nuclease
Ford, Charles E P Evans Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0471
The first of the many significant contributions of Charles Ford (1912±1999) to mammalian cytogenetics was an involvement in the 1956 correction of the human diploid chromosome number. For over 30
Fol d bac k D NA
FMS was isolated in 1983 and was localized to chromosome 5. FMS was shown to code for the colony monocytic stimulating factor-1 receptor (CSF1R) (Sherr et al., 1985). It is expressed in monocytes produced by the bone marrow, where it is required for monocytic differentiation and survival of macrophages, and is also expressed in the spleen, liver, brain, and placenta. v-fms exhibits constitutive tyrosine kinase activity in the absence of ligand and transforms cells. The differences between oncogenic v-fms and normal cellular FMS are a number of scattered point mutations and the replacement of 50 amino acids at the C-terminus of the human gene with 11 unrelated amino acids in the viral gene. The effects of FMS are cell type dependent. In NIH3T3 mouse fibroblast cells the sequence responsible for transformation was localized to amino acid 301 in the extracellular domain. Regulatory sequences at position 969, when mutated, enhance transformation mediated by mutations in codon 301. However, in hematopoietic FDCP-1 cells the 969 mutations transform these cells, rendering them anchorage- independent and tumorigenic in nude mice, whereas the 301 mutant construct is not transforming. Cells infected with the 969 mutant construct cannot be saturated with concentrations of CSF-1 observed to saturate the wild-type receptor (McGlynn et al., 1998). Screening myeloid (pre)leukemia patients for these mutations revealed that mutations at codon 969 were more frequent than those at codon 301 (Ridge et al., 1990; Tobal et al., 1990), suggesting that the FMS oncogene may be involved in the pathogenesis of this disease (see Gallagher et al., 1997 and references therein).
References
Gallagher A, Darley RL and Padua R (1997) The molecular basis of myelodysplastic syndromes. Haematologica 82: 191±204. McDonough SK, Larsen S, Brodey RS, Stock ND and Hardy WD, Jr (1971) A transmissible feline fibrosarcoma of viral origin. Cancer Research 31: 953±956. McGlynn H, Baker AH and Padua RA (1998) Biological consequences of a point mutation at codon 969 of the FMS gene. Leukemia Research 22: 365±372. Ridge SA, Worwood M, Oscier D, Jacobs A and Padua RA (1990) FMS mutations in myelodysplasia, leukaemia and normal subjects. Proceedings of the National Academy of Sciences, USA 87: 1377±1380. Sherr CJ, Rettenmier CW, Sacca R et al. (1985) The c-fms protooncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell 41: 665±676. Tobal K, Pagliuca A, Bhatt B et al. (1990) Mutations of the human FMS gene (M-CSF receptor) in myelodysplastic syndromes and acute myeloid leukemia. Leukemia 4: 486±494.
See also: Cancer Susceptibility; Leukemia
Foldback DNA J H Miller Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0467
Single-stranded DNA with sequences that permit it to make stable secondary structures by folding back upon itself and forming hydrogen bonds.
Follicular Lymphoma P G Isaacson Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1572
Follicular lymphoma is a neoplasm of germinal center B cells that recapitulates the histology of reactive B-cell follicles. It is one of the commonest nonHodgkin's lymphomas in Western countries. Follicular lymphoma is characterized by t(14;18)(q32;q21) that leads to overexpression of the apoptosis inhibitory bcl-2 protein. It is clinically indolent but ultimately incurable. See also: Cancer Susceptibility
Footprinting Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1843
Footprinting is a technique used to identify the binding site of, for example, a protein in a nucleic acid sequence by virtue of the protection given by the binding site against nuclease attack. See also: Nuclease
Ford, Charles E P Evans Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0471
The first of the many significant contributions of Charles Ford (1912±1999) to mammalian cytogenetics was an involvement in the 1956 correction of the human diploid chromosome number. For over 30