A small RNA system ensures accurate homologous pairing and unpaired silencing of meiotic chromosomes.

During meiosis, chromosomes with homologous partners undergo synaptonemal complex (SC)-mediated pairing, while the remaining unpaired chromosomes are heterochromatinized through unpaired silencing. Mechanisms underlying homolog recognition during SC formation are still unclear. Here, we show that the Caenorhabditis elegans Argonaute proteins, CSR-1 and its paralog CSR-2, interacting with 22G-RNAs, are required for synaptonemal complex formation with accurate homology.

Three-dimensional computed tomography image-oriented successful thoracoscopic subtotal esophagectomy for an esophageal cancer patient with an anomalous right superior pulmonary vein: A case report.

Background: Subcarinal lymphadenectomy is an essential procedure in curative esophagectomy for esophageal cancer. The right superior pulmonary vein (RSPV) and its branches are usually located in front of the right main or intermediate bronchus. However, an anomalous posterior branch (aberrant V2) of RSPV passes behind the right intermediate bronchus, where the aberrant V2 may be embedded in the subcarinal nodal packet.

Gefitinib and luteolin cause growth arrest of human prostate cancer PC-3 cells via inhibition of cyclin G-associated kinase and induction of miR-630.

Cyclin G-associated kinase (GAK), a key player in clathrin-mediated membrane trafficking, is overexpressed in various cancer cells. Here, we report that GAK expression is positively correlated with the Gleason score in surgical specimens from prostate cancer patients. Embryonic fibroblasts from knockout mice expressing a kinase-dead (KD) form of GAK showed constitutive hyper-phosphorylation of the epidermal growth factor receptor (EGFR).

Cyclin G-associated kinase regulates protein phosphatase 2A by phosphorylation of its B'γ subunit.

Protein phosphatase 2A (PP2A) bearing the B'γ (=B'α/B56γ1/PR61γ) subunit is recruited to dephosphorylation targets by cyclin G. We demonstrate here that cyclin G-associated kinase (GAK), a component of the GAK/B'γ/cyclin G complex, directly phosphorylates the B'γ-Thr104 residue and regulates PP2A activity. Indeed, an anti-B'γ-pT104 antibody detected immunofluorescence signals at the chromosome and centrosome during mitosis; these signals were reduced by siRNA-mediated GAK knockdown.

Neonatal lethality in knockout mice expressing the kinase-dead form of the gefitinib target GAK is caused by pulmonary dysfunction.

Gefitinib (Iressa) is an inhibitor of the epidermal growth factor receptor (EGFR) that has shown promising activity in the treatment of patients with non-small cell lung cancer (NSCLC). However, adverse side effects of gefitinib treatment, such as respiratory dysfunction, have limited the therapeutic benefit of this targeting strategy. The present results show that this adverse effect can be attributed to the inhibition of the novel gefitinib target GAK (Cyclin G-associated kinase), which is as potently inhibited by the drug as the tyrosine kinase activity of EGFR.