Downregulating Notch counteracts KrasG12D-induced ERK activation and oxidative phosphorylation in myeloproliferative neoplasm

Stress-induced nuclear translocation of CDK5 suppresses neuronal death by downregulating ERK activation via VRK3 phosphorylation

Although extracellular signal-related kinase 1/2 (ERK 1/2) activity is generally associated with cell survival, prolonged ERK activation induced by oxidative stress also mediates neuronal cell death. Here we report that oxidative stress-induced cyclin-dependent kinase 5 (CDK5) activation stimulates neuroprotective signaling via phosphorylation of vaccinia-related kinase 3 (VRK3) at Ser 108. The...

Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants.

Mutations in the calreticulin gene (CALR) represented by deletions and insertions in exon 9 inducing a -1/+2 frameshift are associated with a significant fraction of myeloproliferative neoplasms (MPNs). The mechanisms by which CALR mutants induce MPN are unknown. Here, we show by transcriptional, proliferation, biochemical, and primary cell assays that the pathogenic CALR mutants specifically a...

KrasG12D upregulates Notch signaling to induce gallbladder tumorigenesis in mice

Background Kras mutations and increased Notch activation occur frequently in gallbladder cancer. However, their roles in gallbladder carcinogenesis have not been defined. This study was aimed at determining whether expression of mutant Kras was sufficient to induce gallbladder carcinoma and whether Notch deregulation played a role in this context. Methods We determined Cre recombination activ...

Low-dose methotrexate in myeloproliferative neoplasm models.

Mechanisms of Cr(VI)-induced p53 activation: the role of phosphorylation, mdm2 and ERK.

The present study investigated the molecular mechanisms of p53 activation induced by Cr(VI), using human lung epithelial A549 cells. Cr(VI) increased both protein level and transactivation ability of p53 protein. The activation of p53 is at the protein level instead of the transcriptional level. The degradation of p53 was dramatically decreased upon stimulation by Cr(VI). In addition, Cr(VI) tr...