No abstract

Using a library of siRNAs, we found that ARHGAP18 was essential for the organization of actin stress fibers and focal adhesion. ARHGAP18 is one of the crucial factors for the regulation of RhoA in order to control cell motility and spreading.

Background: Cytokinesis is regulated by phosphorylation and dephosphorylation of proteins. Results: MINK1 associated with STRN4, a regulatory subunit of PP2A, and depletion of either protein inhibited completion of cytokinesis. Conclusion: MINK1 and STRN4 are required for abscission, the final stage of cytokinesis. Significance: Our study reveals novel regulatory mechanisms for abscission.

Medulloblastomas are highly malignant neuroectodermal cerebellar tumors of children. One of the reasons for the difficulty for the treatment of medulloblastomas is their inherent tendency to metastasize through the cerebrospinal fluid (CSF) pathway leading to leptomeningeal dissemination. Recently, genetically modified neural stem cells (NSCs) were shown to have the capability of selectively migrating into glioma mass and delivering therapeutic agents with significant therapeutic benefits. In the present study, we applied the NSC strategy to target medulloblastomas, particularly their leptomeningeal dissemination. We used NSCs that were retrovirally transduced with the cytosine deaminase gene (CD-NSCs). In vitro studies demonstrated that CD-NSCs had sufficient migratory activity toward medulloblastoma cells and exerted a remarkable bystander effect on these cells following the application of 5-fluorocytosine (5-FC). It is noteworthy that neutralization of the hepatocyte growth factor blocked their migration In animal studies using our leptomeningeal dissemination model, CD-NSCs implanted directly into CSF space were shown to distribute diffusely within the disseminated tumor cells and could provide remarkable antitumor effect after intraperitoneal administration of 5-FC. Furthermore, CD-NSC treatment followed by 5-FC administration prolonged survival periods significantly in experimental animals. Our data suggest that the CD-NSC strategy can also be applied to target leptomeningeal dissemination of medulloblastomas.

Proper bioriented attachment of microtubules and kinetochores is essential for the precise distribution of duplicated chromosomes to each daughter cell. An aberrant kinetochore-microtubule attachment results in chromosome instability, which leads to cellular transformation or apoptosis. In this article, we show that ubiquitin-associated protein 2-like (UBAP2L) is necessary for correct kinetochore-microtubule attachment. Depletion of UBAP2L inhibited chromosome alignment in metaphase and delayed progression to anaphase by activating spindle assembly checkpoint signaling. In addition, UBAP2L knockdown increased side-on attachment of kinetochores along the microtubules and suppressed stable kinetochore fiber formation. A proteomics analysis identified protein arginine methyltransferase (PRMT)1 as a direct interaction partner of UBAP2L. UBAP2L has an arginine- and glycine-rich motif called the RGG/RG or GAR motif in the N terminus. Biochemical analysis confirmed that arginine residues in the RGG/RG motif of UBAP2L were directly methylated by PRMT1. Finally, we demonstrated that the RGG/RG motif of UBAP2L is essential for the proper alignment of chromosomes in metaphase for the accurate distribution of chromosomes. Our results show a possible role for arginine methylation in UBAP2L for the progression of mitosis.