Nuclear localization of HTLV-I bZIP factor (HBZ) is mediated by three distinct motifs.
The genome of the human T-cell leukemia virus type I (HTLV-I) codes for a basic leucine zipper protein, HBZ, capable of repressing JUN activity and viral transcription. Transient expression in mammalian cells showed that HBZ was targeted to the nucleus, where it accumulated in nuclear speckles. By using a complementary set of deletion mutants, we report here that the nuclear targeting of HBZ is mediated by three distinct nuclear localization signals and that at least two are necessary for the translocation of HBZ to the nucleus. Moreover, the resulting mutant proteins distribute throughout the nucleoplasm and/or into the nucleoli, whereas the wild-type HBZ exclusively accumulates in nuclear speckles, suggesting that the integrity of the protein is required for its speckle localization. We also demonstrate that the HBZ-containing speckles do not correspond to Cajal bodies, splicing factor compartments, or promyelocytic leukemia oncoprotein bodies. Unexpectedly, by using immunogold electron microscopy, we found HBZ localized to heterochromatin. Until now, such characteristics had never been described for a transcription factor and could explain the inhibitory activity of HBZ.
Hivin
Patrick
P
Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS/UM I UMR 5121/IFR 122, Institut de Biologie, 34960 Montpellier Cedex 2, France.
Frédéric
Mélissa
M
Arpin-André
Charlotte
C
Basbous
Jihane
J
Gay
Bernard
B
Thébault
Sabine
S
Mesnard
Jean-Michel
JM
D020816:Amino Acid Motifs / Q000502:physiology*; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D019556:COS Cells; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D022003:Cell Nucleus Structures / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008854:Microscopy, Electron / Q000379:methods; D009154:Mutation; D019913:Nuclear Localization Signals / Q000235:genetics / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012191:Retroviridae Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D050976:Basic-Leucine Zipper Transcription Factors; C479751:HBZ protein, human T-cell leukemia virus type I; D006570:Heterochromatin; D019913:Nuclear Localization Signals; D016755:Proto-Oncogene Proteins c-jun; D012191:Retroviridae Proteins; D014157:Transcription Factors; D014764:Viral Proteins