Tyrosine phosphorylation regulates cell cycle-dependent nuclear localization of Cdc48p.
Cdc48p from Saccharomyces cerevisiae and its highly conserved mammalian homologue VCP (valosin-containing protein) are ATPases with essential functions in cell division and homotypic fusion of endoplasmic reticulum vesicles. Both are mainly attached to the endoplasmic reticulum, but relocalize in a cell cycle-dependent manner: Cdc48p enters the nucleus during late G1; VCP aggregates at the centrosome during mitosis. The nuclear import signal sequence of Cdc48p was localized near the amino terminus and its function demonstrated by mutagenesis. The nuclear import is regulated by a cell cycle-dependent phosphorylation of a tyrosine residue near the carboxy terminus. Two-hybrid studies indicate that the phosphorylation results in a conformational change of the protein, exposing the nuclear import signal sequence previously masked by a stretch of acidic residues.
Madeo
F
F
Physiologisch-chemisches Institut der Universität Tübingen, Germany.
Schlauer
J
J
Zischka
H
H
Mecke
D
D
Fröhlich
K U
KU
D000251:Adenosine Triphosphatases; D000650:Amnion / Q000166:cytology; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D016254:Mutagenesis, Insertional; D019913:Nuclear Localization Signals / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D019913:Nuclear Localization Signals; D029701:Saccharomyces cerevisiae Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; C000614178:VCP protein, human; D000074405:Valosin Containing Protein