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. Author manuscript; available in PMC: 2010 Apr 1.
Published in final edited form as: Cancer Res. 2009 Mar 24;69(7):2817–2825. doi: 10.1158/0008-5472.CAN-08-4182

Figure 6. Proposed model of the effect of subcellular localization on cyclin E stability and activity in normal versus tumor cells.

Figure 6

A, in normal cells, EL shuttles between the nucleus and cytoplasm (arrows). Nuclear import is faster than export causing EL/Cdk2 to accumulate in the nucleus where nuclear Fbw7 can target EL for degradation. EL shuttling results in a net loss of protein from both subcellular compartments. B, EL shows similar subcellular distribution patterns and targeting by Fbw7 in tumor cells as outlined for normal cells. LMW-E and LMW-E/Cdk2 preferentially accumulate in the cytoplasm due to lack of the nuclear localization sequence and altered shuttling dynamics (arrows) and have reduced susceptibility to nuclear Fbw7. Finally, tumor cells have higher cyclin E–associated kinase activity in the cytoplasm than do normal cells because tumor cells accumulate EL/Cdk2 and tumor-specific LMW-E/Cdk2 in the cytoplasm.