Kinesin-14 motor protein KIFC1 participates in DNA synthesis and chromatin maintenance

Abstract

The nuclear localization signal (NLS) in kinesin-14 KIFC1 is associated with nuclear importins and Ran gradient, but detailed mechanism remains unknown. In this study, we found that KIFC1 proteins have specific transport characteristics during cell cycle. In the absence of KIFC1, cell cycle kinetics decrease significantly with a prolonged S phase. After KIFC1 overexpression, the duration of S phase becomes shorten. KIFC1 may transport the recombinant/replicate-related proteins into the nucleus, meanwhile avoiding excessive KIFC1 in the cytoplasm, which results in aberrant microtubule bundling. Interestingly, the deletion of kifc1 in human cells results in a higher ratio of aberrant nuclear membrane, and the degradation of lamin B and lamin A/C. We also found that kifc1 deletion leads to defects in metaphase mitotic spindle assembly, and then results in chromosome structural abnormality. The kifc1 -/- cells finally form micronuclei in daughter cells, and results in aneuploidy and chromosome loss in cell cycle. In this study, we demonstrate that kinesin-14 KIFC1 proteins involve in regulating DNA synthesis in S phase, and chromatin maintenance in mitosis, and maintain cell growth in a nuclear transport-independent way.

The ATM and ATR kinases regulate centrosome clustering and tumor recurrence by targeting KIFC1 phosphorylation

“…KIFC1 is also associated with nuclear importins 40 , 41 and an acentrosomal spindle organization 42 . Thus, we further analyzed the influence of KIFC1-S26 phosphorylation on cell cycle progression (Fig.…”

“…Thus, we further analyzed the influence of KIFC1-S26 phosphorylation on cell cycle progression (Fig. S7a ) 40 , nuclear membrane (Fig. S7b ) 40 , and acentrosomal poles (Fig.…”

Double Duty: Mitotic Kinesins and Their Post-Mitotic Functions in Neurons

“…In mammals, the Kinesin-14 family includes three kinesins: KIF1C, KIF2C, and KIF3C [ 26 ]. During interphase, KIFC1/HSET is sequestered to the nucleus due to its nuclear localization signal (NLS) to prevent aberrant MT crosslinking [ 27 , 28 ]. During mitosis, KIF1C is released to the cytoplasm where it controls MT crosslinking and sliding [ 27 ].…”

KIFC1 is essential for normal spermatogenesis and its depletion results in early germ cell apoptosis in the Kuruma shrimp, Penaeus (Marsupenaeus) japonicus

“…The KIFC1 deficiency affects the normal mitosis, as well as damages cell growth, proliferation and survival. Wei and Yang [47] found that the KIFC1 knockout 293T cells are hard to heal from scratched mechanical damage and cell death occurs in the wound healing assay. In KIFC1-depleted IMR-90 cells, although no obvious immediate cell death was observed, 20% less cells were detected compared with control group.…”