Over-expression of the HIV-1 Rev promotes death of nondividing eukaryotic cells.
Expression of the human immunodeficiency virus type 1 (HIV-1) Rev protein is essential for completion of the viral life cycle. Rev mediates nuclear export of partially spliced and unspliced viral transcripts and therefore bears a nuclear localization signal (NLS) as well as a nuclear export signal (NES), which allow its nucleocytoplasmic shuttling. Attempts to express the wild-type Rev protein in eukaryotic human cultured cells have encountered difficulties and so far have failed. Here we show that accumulation of Rev, which occurs in nondividing Rev-expressing cells or when such cells reach confluency, results in death of these cells. Cell death was also promoted by addition of a cell permeable peptide bearing the Rev-NES sequence, but not by the Rev-NLS peptide. Our results probably indicate that binding of excess amounts of the Rev protein or the NES peptide to the exportin receptor CRM1 results in cells' death.
Levin
Aviad
A
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Hayouka
Zvi
Z
Friedler
Assaf
A
Loyter
Abraham
A
D016923:Cell Death; D002460:Cell Line; D005057:Eukaryotic Cells / Q000821:virology*; D015870:Gene Expression; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism*; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D037521:Virulence Factors / Q000096:biosynthesis*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis*; D000097606:Exportin 1 Protein
D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D037521:Virulence Factors; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein; C514860:rev protein, Human Immunodeficiency Virus-1