12 research outputs found
Targeting sphingosine kinase 2 (SphK2) by ABC294640 inhibits colorectal cancer cell growth in vitro and in vivo
Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation
Ulcerative colitis that developed during radiotherapy for prostate cancer, deteriorated rapidly and required emergency surgery
Phosphoregulation and depolymerization-driven movement of the Dam1 complex do not require ring formation
Overlapping kinetochore targets of CK2 and Aurora B kinases in mitotic regulation
CK2 associates with kinetochore protein Mif2/CENP-C. Loss of CK2 results in defects in chromosome segregation, short mitotic spindle, and activation of the spindle assembly checkpoint. CK2 phosphorylates Mif2 and Ndc10. CK2 phosphorylation plays antagonistic and synergistic roles with Aurora B phosphorylation of Mif2 and Ndc10, respectively
Investigating Chaperonin-Containing TCP-1 subunit 2 as an essential component of the chaperonin complex for tumorigenesis
Ringing the changes: emerging roles for DASH at the kinetochore–microtubule Interface
Regulated interaction between kinetochores and the mitotic spindle is essential for the fidelity of chromosome segregation. Potentially deleterious attachments are corrected during prometaphase and metaphase. Correct attachments must persist during anaphase, when spindle-generated forces separate chromosomes to opposite poles. In yeast, the heterodecameric DASH complex plays a vital pole in maintaining this link. In vitro DASH forms both oligomeric patches and rings that can form load-bearing attachments with the tips of polymerising and depolymerising microtubules. In vivo, DASH localises primarily at the kinetochore, and has a role maintaining correct attachment between spindles and chromosomes in both Saccharomyces cerevisiae and Schizosaccharomyces pombe. Recent work has begun to describe how DASH acts alongside other components of the outer kinetochore to create a dynamic, regulated kinetochore-microtubule interface. Here, we review some of the key experiments into DASH function and discuss their implications for the nature of kinetochore-microtubule attachments in yeast and other organisms
Sphingosine kinase 2 activates autophagy and protects neurons against ischemic injury through interaction with Bcl-2 via its putative BH3 domain
Challenging Proteostasis: Role of the Chaperone Network to Control Aggregation-Prone Proteins in Human Disease
Protein homeostasis (Proteostasis) is essential for correct and efficient protein function within the living cell. Among the critical components of the Proteostasis Network (PN) are molecular chaperones that serve widely in protein biogenesis under physiological conditions, and prevent protein misfolding and aggregation enhanced by conditions of cellular stress. For Alzheimer’s, Parkinson’s, Huntington’s diseases and ALS, multiple classes of molecular chaperones interact with the highly aggregation-prone proteins amyloid-β, tau, α-synuclein, huntingtin and SOD1 to influence the course of proteotoxicity associated with these neurodegenerative diseases. Accordingly, overexpression of molecular chaperones and induction of the heat shock response have been shown to be protective in a wide range of animal models of these diseases. In contrast, for cancer cells the upregulation of chaperones has the undesirable effect of promoting cellular survival and tumor growth by stabilizing mutant oncoproteins. In both situations, physiological levels of molecular chaperones eventually become functionally compromised by the persistence of misfolded substrates, leading to a decline in global protein homeostasis and the dysregulation of diverse cellular pathways. The phenomenon of chaperone competition may underlie the broad pathology observed in aging and neurodegenerative diseases, and restoration of physiological protein homeostasis may be a suitable therapeutic avenue for neurodegeneration as well as for cancer