期刊
JOURNAL OF CELL BIOLOGY
卷 181, 期 3, 页码 485-496出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200801047
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- NCI NIH HHS [R37 CA076584, R21-CA125173, R37-CA76584, CA116034, R01 CA116034, R21 CA125173, R01 CA118495, CA118495] Funding Source: Medline
- NIGMS NIH HHS [GM55279, R01-GM57587, R01 GM055279, R01 GM057587] Funding Source: Medline
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.
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