A cis-acting peptide signal in human immunodeficiency virus type I Rev which inhibits nuclear entry of small proteins.
A peptide signal, which may control nucleo-cytoplasmic protein trafficking, was newly identified in human immunodeficiency virus type I (HIV-1) Rev, a lentiviral post-transcriptional transactivator. The sequence, in the amino-terminal portion of HIV-1 Rev, maintains a Rev mutant with a dysfunctional nuclear/nucleolar targeting signal outside of the nucleus, although this Rev molecule itself is small enough to pass through the nuclear pores. Transition of this sequence to the N-terminus of human T-lymphocytic leukemia/lymphoma virus type I (HTLV-I) p21x, which is usually located evenly distributed throughout the cell, resulted in capture of p21x in the cytoplasm. Mutational analysis clarified that a 14 residue peptide sequence was sufficient to display this inhibitory effect against nuclear entry. Furthermore, this HIV-1 Rev sequence was capable of inhibiting nuclear entry of a fragment of a human ribosomal protein, when it was fused to the carboxy terminus. The identified nuclear entry inhibitory signal (NIS) contains a conserved hydrophilicity motif, which forms an amphipathic helix. Significantly, this motif and its helical structure were shown to be important for NIS function and the HIV-1 Rev function itself. Possible roles for NIS as a molecular anchor are proposed herein.
Kubota
S
S
Center for Human Virology, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Pomerantz
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D017124:Conserved Sequence; D003593:Cytoplasm / Q000378:metabolism; D015694:Gene Products, rev / Q000737:chemistry / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000235:genetics; D017354:Point Mutation; D021382:Protein Sorting Signals / Q000737:chemistry / Q000502:physiology*; D017433:Protein Structure, Secondary; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000502:physiology; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D019913:Nuclear Localization Signals; D021382:Protein Sorting Signals; C489168:RPS25 protein, human; D015682:Retroviridae Proteins, Oncogenic; D012269:Ribosomal Proteins; C072341:p21X protein, Human T-lymphotropic virus 1; D054321:rev Gene Products, Human Immunodeficiency Virus