Genotoxic stress and cellular stress alter the subcellular distribution of human T-cell leukemia virus type 1 tax through a CRM1-dependent mechanism.
Human T-cell leukemia virus type 1 Tax is a predominantly nuclear viral oncoprotein that colocalizes with cellular proteins in nuclear foci known as Tax speckled structures (TSS). Tax is also diffusely distributed throughout the cytoplasm, where it interacts with and affects the functions of cytoplasmic cellular proteins. Mechanisms that regulate the distribution of Tax between the cytoplasm and nucleus remain to be identified. Since Tax has been shown to promote genome instability by perturbing cell cycle progression and DNA repair mechanisms following DNA damage, we examined the effect of genotoxic stress on the subcellular distribution and interacting partners of Tax. Tax localization was altered in response to various forms of cellular stress, resulting in an increase in cytoplasmic Tax and a decrease in Tax speckled structures. Concomitantly, colocalization of Tax with sc35 (a TSS protein) decreased following stress. Tax translocation required the CRM1 nuclear export pathway, and a transient interaction between Tax and CRM1 was observed following stress. These results suggest that the subcellular distribution of Tax and the interactions between Tax and cellular proteins respond dynamically to cellular stress. Changes in Tax distribution and interacting partners are likely to affect cellular processes that regulate cellular transformation.
Gatza
Michael L
ML
Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza MS-385, Houston, TX 77030, USA.
Marriott
Susan J
SJ
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000528:radiation effects; D000818:Animals; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000187:drug effects / Q000528:radiation effects; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D005720:Gamma Rays; D016356:Gene Products, tax / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D042581:Intranuclear Space / Q000378:metabolism / Q000821:virology; D028884:Karyopherins / Q000378:metabolism*; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014466:Ultraviolet Rays; D000097606:Exportin 1 Protein
D016356:Gene Products, tax; D028884:Karyopherins; D009153:Mutagens; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein