Deregulated expression of the RanBP1 gene alters cell cycle progression in murine fibroblasts.
RanBP1 is a molecular partner of the Ran GTPase, which is implicated in the control of several processes, including DNA replication, mitotic entry and exit, cell cycle progression, nuclear structure, protein import and RNA export. While most genes encoding Ran-interacting partners are constitutively active, transcription of the RanBP1 mRNA is repressed in non proliferating cells, is activated at the G1/S transition in cycling cells and peaks during S phase. We report here that forced expression of the RanBP1 gene disrupts the orderly execution of the cell division cycle at several stages, causing inhibition of DNA replication, defective mitotic exit and failure of chromatin decondensation during the telophase-to-interphase transition in cells that achieve nuclear duplication and chromosome segregation. These results suggest that deregulated RanBP1 activity interferes with the Ran GTPase cycle and prevents the functioning of the Ran signalling system during the cell cycle.
Battistoni
A
A
National Research Council Center of Evolutionary Genetics, University of Rome 'La Sapienza', Italy.
Guarguaglini
G
G
Degrassi
F
F
Pittoggi
C
C
Palena
A
A
Di Matteo
G
G
Pisano
C
C
Cundari
E
E
Lavia
P
P
D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008938:Mitosis / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D016196:S Phase / Q000235:genetics; D020931:ran GTP-Binding Protein
D016895:Culture Media, Serum-Free; D009687:Nuclear Proteins; C091775:ran-binding protein 1; D019204:GTP-Binding Proteins; D020931:ran GTP-Binding Protein