Forsdyke Laboratory of Bioinformatics and Theoretical Biology
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| Keywords: Bioinformatics, Genomics, Theoretical Biology, Speciation, AIDS, Isochores, Evolution, Biohistory, Darwin, Butler, Romanes, Bateson, Goldschmidt, Chargaff, Wada, G0/G1 switch genes (G0S genes), Immunology, Malaria |
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Department of Biochemistry, Botterell Hall, Queen's University, Kingston, Ontario, Canada, K7L3N6.
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After activation by the plant lectin, concanavalin A (Con-A), T lymphocytes enter G1 phase and enlarge, subsequently entering S phase and dividing. A set of human putative G0/G1 switch regulatory genes ("G0S" genes) were identified in our laboratory. The corresponding mRNAs were found to be differentially expressed in human blood lymphocytes shortly after the addition of Con-A. It was anticipated that such mRNAs would correspond to proteins involved in orchestrating either entry into the G1 phase of the cell cycle, or the immediate defence response to a foreign pathogen. Some of the genes have been found to play a general role in signal transmisssion, e.g. in the central nervous system (Click here). The 8 genes selected for detailed analysis were G0S2, G0S3, G0S7, G0S8, G0S9, G0S19, G0S24 and G0S30. G0S2 is very sensitive to the immunosuppressant, cyclosporin-A. G0S3 and G0S7 are members of the FOS oncogene family. G0S8 has been renamed RGS2 (regulator of G-protein signalling number 2), although it also reacts with adenyl cyclase. G0S19, which we reported in 1985 as a differentially expressed mRNA, corresponds to the chemokine MIP1alpha (or CCL3), the receptor for which (CCR5) is a co-receptor for HIV-1. Resistance to AIDS is correlated with copy numbers of G0S19/CCL3 and related genes . G0S24 by virtue of its binding to AU-rich elements, destabilises HIV-1 RNA and tumor necrosis factor alpha (TNFalpha) mRNA, and thus may prove important for AIDS therapy (Click Here). G0S30, which we also reported in 1985, corresponds to the murine EGR1 and rat NGF1A genes. These encode a transcription factor that regulates TNFalpha and cell senescence, and is a "gatekeeper" of the p53 tumor suppressor pathway. Some of the human genes have acquired names originally applied to the rodent homologs. |
| Human G0 Switch Gene |
Rodent Homolog |
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G0S2 |
. |
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G0S3/FOSB |
FOSB |
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G0S7/FOS |
FOS/TIS28 |
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G0S8/RGS2 |
RGS2 |
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G0S9/PBEF |
. |
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G0S19/MIP1-alpha/CCL3 |
MIP1-alpha/LD78-alpha/464.1/CCL3 |
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G0S24 |
TIS11/NUP475/TTP (TrisTetraProlin) |
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G0S30/EGR1 |
EGR1/NGFI-A/TIS8/ZIF-268 |
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