Rac1 accumulates in the nucleus during the G2 phase of the cell cycle and promotes cell division.
Rac1 regulates a wide variety of cellular processes. The polybasic region of the Rac1 C terminus functions both as a plasma membrane-targeting motif and a nuclear localization sequence (NLS). We show that a triproline N-terminal to the polybasic region contributes to the NLS, which is cryptic in the sense that it is strongly inhibited by geranylgeranylation of the adjacent cysteine. Subcellular fractionation demonstrated endogenous Rac1 in the nucleus and Triton X-114 partition revealed that this pool is prenylated. Cell cycle-blocking agents, synchronization of cells stably expressing low levels of GFP-Rac1, and time-lapse microscopy of asynchronous cells revealed Rac1 accumulation in the nucleus in late G2 and exclusion in early G1. Although constitutively active Rac1 restricted to the cytoplasm inhibited cell division, activated Rac1 expressed constitutively in the nucleus increased the mitotic rate. These results show that Rac1 cycles in and out of the nucleus during the cell cycle and thereby plays a role in promoting cell division.
Michaelson
David
D
Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
Abidi
Wasif
W
Guardavaccaro
Daniele
D
Zhou
Mo
M
Ahearn
Ian
I
Pagano
Michele
M
Philips
Mark R
MR
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D016195:G2 Phase / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D054876:Prenylation; D011392:Proline / Q000378:metabolism; D017368:Protein Prenylation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D019913:Nuclear Localization Signals; D011993:Recombinant Fusion Proteins; D011392:Proline; D020830:rac1 GTP-Binding Protein