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.
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Aviad
A
Levin
Zvi
Z
Hayouka
Assaf
A
Friedler
Abraham
A
Loyter
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