Stabilization of Cyclin-Dependent Kinase 4 by Methionyl-tRNA Synthetase in p16INK4a-Negative Cancer.

Although abnormal increases in the level or activity of cyclin-dependent kinase 4 (CDK4) occur frequently in cancer, the underlying mechanism is not fully understood. Here, we show that methionyl-tRNA synthetase (MRS) specifically stabilizes CDK4 by enhancing the formation of the complex between CDK4 and a chaperone protein. Knockdown of MRS reduced the CDK4 level, resulting in G0/G1 cell cycle arrest. The effects of MRS on CDK4 stability were more prominent in the tumor suppressor p16INK4a-negative cancer cells because of the competitive relationship of the two proteins for binding to CDK4. Suppression of MRS reduced cell transformation and the tumorigenic ability of a p16INK4a-negative breast cancer cell line in vivo. Further, the MRS levels showed a positive correlation with those of CDK4 and the downstream signals at high frequency in p16INK4a-negative human breast cancer tissues. This work revealed an unexpected functional connection between the two enzymes involving protein synthesis and the cell cycle.

Utility of the Montreal Cognitive Assessment (MoCA) and its subset in HIV-associated neurocognitive disorder (HAND) screening.

OBJECTIVES: The Montreal Cognitive Assessment (MoCA) is a useful screening tool for mild cognitive impairment. We aimed to know whether the full MoCA and subsets of the full test are effective for detecting HIV-associated neurocognitive disorder (HAND). METHODS: We examined the socio-demographic, clinical, functional, and neuropsychological levels of 194 HIV-infected patients. We compared total scores and scores from each cognitive domain of MoCA between patients with and without HAND. We also examined the utility of subsets of the full test using a few selective domains. The diagnostic accuracies of MoCA and subset composition were evaluated. RESULTS: The total scores of MoCA (P<0.001) and scores from Trail Making Test-B (P=0.020), attention domain (P=0.005), and immediate (P=0.003) and delayed recall (P=0.002) differed between patients with and without HAND. A subset composed of Trail Making Test-B, rescored serial subtraction, and immediate/delayed recall showed a 69.2% accuracy. CONCLUSIONS: Our results suggest that the MoCA and its subsets alone are not sufficient in screening for HAND. Further studies will be needed to develop a simpler and easier screening tool for HAND based on this study.