Biology subjects

Vicente, J. J.

Publications and source records attributed to Vicente, J. J..

3 recordsLinked to original sources

bioRxiv2025

MCAK/Kif2C centromeric activity level tunes K-fiber stability.

MCAK/Kif2C is a microtubule-depolymerizing kinesin implicated in the correction of chromosome attachment errors. When eliminated from kinetochores, cells exhibit delayed congression and a modest increase in chromosome missegregation. Curiously, MCAK/Kif2C overexpression (OE) promotes these same defects. Both depletion and excess levels of centromeric MCAK/Kif2C increase acetylated tubulin levels in the spindle, suggesting an increase in k-fiber stability. We conclude that this is the likely mechanism for the increase in chromosome segregation errors observed in both of these antagonistic conditions. Reduced MCAK/Kif2C increased the tubulin ratio on the two faces of the kinetochore, suggesting a greater likelihood of erroneous lateral MT interactions. In contrast, excess MCAK/Kif2C reduced the tubulin ratio at the kinetochore, stabilizing end-on MT interactions that increase the IKD and ultimately culminate in excessive stabilization of K-fiber microtubules. Both of these conditions promote chromosome segregation errors. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/638494v2_ufig1.gif" ALT="Figure 1"> View larger version (87K): org.highwire.dtl.DTLVardef@108570org.highwire.dtl.DTLVardef@a891a3org.highwire.dtl.DTLVardef@f1761borg.highwire.dtl.DTLVardef@811c70_HPS_FORMAT_FIGEXP M_FIG C_FIG In briefCell biology; Chromosome organization HighlightsO_LIAn optimal level of MCAK/Kif2C ensures error-correction during mitosis C_LIO_LIBoth excess or insufficient MCAK/Kif2C suppresses MT turnover in k-fibers C_LIO_LIExcess MCAK/Kif2C deforms kinetochores with uncoordinated movement C_LIO_LIInsufficient MCAK/Kif2C deforms kinetochores with unresolved lateral MTs C_LI

cell biology↗

bioRxiv2024

The kinesin motor Kif9 regulates centriolar satellite positioning and mitotic progression.

Centrosomes are the principal microtubule-organizing centers of the cell and play an essential role in mitotic spindle function. Centrosome biogenesis is achieved by strict control of protein acquisition and phosphorylation prior to mitosis. Defects in this process promote fragmentation of pericentriolar material culminating in multipolar spindles and chromosome missegregation. Centriolar satellites, membrane-less aggrupations of proteins involved in the trafficking of proteins toward and away from the centrosome, are thought to contribute to centrosome biogenesis. Here we show that the microtubule plus-end directed kinesin motor Kif9 localizes to centriolar satellites and regulates their pericentrosomal localization during interphase. Lack of Kif9 leads to aggregation of satellites closer to the centrosome and increased centrosomal protein degradation that disrupts centrosome maturation and results in chromosome congression and segregation defects during mitosis. Our data reveal roles for Kif9 and centriolar satellites in the regulation of cellular proteostasis and mitosis.

cell biology↗

bioRxiv2023

Mitosis exit followed by death in interphase prevents the development of polyploid giant cancer cells.

Microtubule targeting agents (MTAs) are commonly prescribed to treat cancers and predominantly kill cancer cells in mitosis. Significantly, some MTA-treated cancer cells can escape death in mitosis and exit mitosis, and become malignant polyploid giant cancer cells (PGCC). Considering the low number of malignant cells undergoing mitosis in tumor tissue, killing these cells in interphase may represent a favored antitumor approach. We discovered that ST-401, a mild inhibitor of microtubule assembly, preferentially kills cancer cells in interphase as opposed to mitosis, and avoids the development of PGCC. Single cell RNA sequencing identified mRNA transcripts regulated by ST-401, including mRNAs involved in ribosome and mitochondrial functions. Accordingly, ST-401 induces an integrated stress response and promotes mitochondria fission accompanied by a reduction in energy metabolism. This cell response may underly death in interphase and avoid the development of PGCC.

cell biology↗