HTLV-I Tax and cell cycle progression.
Human T-cell leukemia virus type I (HTLV-I) is the etiological agent for adult T-cell leukemia (ATL) and various human myopathies/neuropathies. HTLV-I encodes a 40 kDa phosphoprotein, Tax, which has been implicated in cellular transformation. In similarity with several other oncoproteins such as Myc, Jun, and Fos, Tax is a transcriptional activator. How Tax mechanistically dysregulates the cell cycle remains unclear. Recent findings from us and others have shown that Tax targets key regulators of G1/S and M progression such as p16INK4a, cyclin D1, cyclin D3-cdk, and the mitotic spindle checkpoint apparatus. Thus, Tax influences the progression of cells in various phases of the cell cycle. In this regard, we will discuss three distinct mechanisms through which Tax affects cell-cycling: a) through direct association Tax can abrogate the inhibitory function of p16INK4a on the G1-cdks, b) Tax can also directly influence cyclin D-cdk activities by a protein-protein interaction, and c) Tax targets the HsMAD1 mitotic spindle-assembly checkpoint protein. Through these varied routes, the HTLV-I oncoprotein dysregulates cellular growth controls and engenders a proclivity of cells toward a loss of DNA-damage surveillance.
Neuveut
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Laboratoire de Recombinaison et Expression Genetique, Institut Pasteur, Paris, France.
Jeang
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KT
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D019938:Cyclin D1 / Q000378:metabolism; D056743:Cyclin D3; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins / Q000378:metabolism; D016356:Gene Products, tax / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D008938:Mitosis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
C534696:CCND3 protein, human; D002352:Carrier Proteins; D056743:Cyclin D3; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins; D016356:Gene Products, tax; D019938:Cyclin D1