Mutations in the nuclear export signal of human ran-binding protein RanBP1 block the Rev-mediated posttranscriptional regulation of human immunodeficiency virus type 1.
We identified a region in the human Ran GTPase-binding protein RanBP1 that shares similarities to the nuclear export signal of the inhibitor of the cAMP-dependent protein kinase. Mutational analysis confirmed that this region is responsible for the cytoplasmic accumulation of RanBP1 and can functionally replace the nuclear export signal of Rev of human immunodeficiency virus type 1. We showed that RanBP1 interferes with Rev-mediated expression of human immunodeficiency virus type 1, whereas the RanBP1 with inactivated nuclear export signal abrogates Rev function. Expression of a Rev-independent molecular clone, which is regulated via the constitutive transport element (CTE) of the simian retrovirus type 1, is not affected. These findings indicate that Rev and RanBP1 compete for the same nuclear export pathway, whereas Rev- and the CTE-mediated pathways are distinct. The inhibition of Rev function is independent of the ability of RanBP1 to associate with Ran and therefore, it is not likely a result of interference with Ran function. These data suggest that RanBP1 interacts with Rev at the putative nuclear receptor and, hence, shares a step in posttranscriptional pathway with Rev.
Zolotukhin
A S
AS
Human Retrovirus Pathogenesis Group, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Frederick, Maryland 21702-1201, USA.
Felber
B K
BK
D000595:Amino Acid Sequence; D001692:Biological Transport / Q000235:genetics; D002451:Cell Compartmentation / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism*; D004252:DNA Mutational Analysis; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D015694:Gene Products, rev / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D021382:Protein Sorting Signals; D012323:RNA Processing, Post-Transcriptional; D017386:Sequence Homology, Amino Acid; D020931:ran GTP-Binding Protein; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D009687:Nuclear Proteins; D021382:Protein Sorting Signals; C091775:ran-binding protein 1; D054321:rev Gene Products, Human Immunodeficiency Virus; D019204:GTP-Binding Proteins; D020931:ran GTP-Binding Protein