Migratory Localization of Cyclin D2-Cdk4 Complex Suggests a Spatial Regulation of the G1-S Transition

Abstract

ABSTRACT. The association of the cyclin D-Cdk (DC) complex with retinoblastoma protein (pRb) is required for the G1-S transition of the cell cycle. Cyclin synthesis, nuclear localization and degradation are control mechanisms for the transition, but regulation of the DC complex nuclear import also contributes to the transition. Analysis of the timing of the G1-S transition in mammalian cell lines revealed acceleration with overexpression of cyclin D2 and Cdk4. Immunolocalization assays revealed that cyclin D2 and Cdk4 formed a complex in the cytoplasm and approached the nucleus. They accumulated on the cytosolic surfaces of the nuclear pores and then were arrested at the nuclear membrane before the nucleus reached a critical size. Finally, the complex was released into the nucleus and colocalized with pRb there, which led to pRb phosphorylation and DNA synthesis. The translocalization depended on the G1-S transition. In contrast, a truncated cyclin D2 that was not able to fully associate with Cdk4 lost the ability for release into the nucleus. This pattern of translocalization suggests a spatial separation of the cyclin D-Cdk complex from pRb and DNA in the nucleus to regulate the G1-S transition.

T-type voltage-activated calcium channel Cav3.1, but not Cav3.2, is involved in the inhibition of proliferation and apoptosis in MCF-7 human breast cancer cells

“…Furthermore, in our study, Ca v 3.1 knockdown resulted in increases in the expressions of MIS12, SYCP1 and CCND2 (which are thought to be involved in cell cycle progression) (42)(43)(44). Consequently, Ca v 3.1 may also suppress the cell cycle, thus inhibiting proliferation.…”

Long noncoding RNA linc00598 regulates CCND2 transcription and modulates the G1 checkpoint

“…It has been reported that the CCND2/CDK4/p27 complex is required for nuclear translocation of CCND236. Since the expression levels of CDK4 and p27 were not influenced in shlinc00598 stable HEK293t cell lines (Supplementary Fig.…”

LAP3 promotes glioma progression by regulating proliferation, migration and invasion of glioma cells

“…G1/S phase transition is a major checkpoint for cell cycle progression [26]. Therefore, CDK2 and cyclin D2 were examined, CDK2 and cyclin D2 are the critical differently positive regulators during this transition [27,28]. Western blotting assay showed that CDK2 and cyclin D2 were partly suppressed in the siRNALAP3 group in the U87 and U251 cells.…”