Autophagy is a crucial component of the cellular stress adaptation response that maintains mammalian homeostasis. Autophagy protects against neurodegenerative and inflammatory conditions, aging, and cancer. This is accomplished by the degradation and intracellular recycling of cellular components to maintain energy metabolism and by damage mitigation through the elimination of damaged proteins and organelles. How autophagy modulates oncogenesis is gradually emerging. Tumor cells induce autophagy in response to metabolic stress to promote survival, suggesting deployment of therapeutic strategies to block autophagy for cancer therapy. By contrast, defects in autophagy lead to cell death, chronic inflammation, and genetic instability. Thus, stimulating autophagy may be a powerful approach for chemoprevention. Analogous to infection or toxins that create persistent tissue damage and chronic inflammation that increases the incidence of cancer, defective autophagy represents a cell-intrinsic mechanism to create the damaging, inflammatory environment that predisposes to cancer. Thus, cellular damage mitigation through autophagy is a novel mechanism of tumor suppression.

DNA-responsive checkpoints prevent cell-cycle progression following DNA damage or replication inhibition. The mitotic activator Cdc25 is suppressed by checkpoints through inhibitory phosphorylation at Ser287 (Xenopus numbering) and docking of 14-3-3. Ser287 phosphorylation is a major locus of G2/M checkpoint control, although several checkpoint-independent kinases can phosphorylate this site. We reported previously that mitotic entry requires 14-3-3 removal and Ser287 dephosphorylation. We show here that DNA-responsive checkpoints also activate PP2A/B56delta phosphatase complexes to dephosphorylate Cdc25 at a site distinct from Ser287 (T138), the phosphorylation of which is required for 14-3-3 release. However, phosphorylation of T138 is not sufficient for 14-3-3 release from Cdc25. Our data suggest that creation of a 14-3-3 "sink," consisting of phosphorylated 14-3-3 binding intermediate filament proteins, including keratins, coupled with reduced Cdc25-14-3-3 affinity, contribute to Cdc25 activation. These observations identify PP2A/B56delta as a central checkpoint effector and suggest a mechanism for controlling 14-3-3 interactions to promote mitosis.

Constant Cyclin B levels are maintained during a CSF arrest through the regulation of Emi2 activity. A balance between Cdc2 and PP2A controls Emi2 phosphorylation, which in turn controls the ability of Emi2 to bind to and inhibit the APC. This balance allows proper maintenance of Cyclin B levels and Cdc2 kinase activity during CSF arrest.

Before fertilization, vertebrate eggs are arrested in meiosis II by cytostatic factor (CSF), which holds the anaphase-promoting complex (APC) in an inactive state. It was recently reported that Mos, an integral component of CSF, acts in part by promoting the Rsk-mediated phosphorylation of the APC inhibitor Emi2/Erp1. We report here that Rsk phosphorylation of Emi2 promotes its interaction with the protein phosphatase PP2A. Emi2 residues adjacent to the Rsk phosphorylation site were important for PP2A binding. An Emi2 mutant that retained Rsk phosphorylation but lacked PP2A binding could not be modulated by Mos. PP2A bound to Emi2 acted on two distinct clusters of sites phosphorylated by Cdc2, one responsible for modulating its stability during CSF arrest and one that controls binding to the APC. These findings provide a molecular mechanism for Mos action in promoting CSF arrest and also define an unusual mechanism, whereby protein phosphorylation recruits a phosphatase for dephosphorylation of distinct sites phosphorylated by another kinase.

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The aim of this study was to examine the effects of a 12-week home-based exercise program on physical function, psychological dimensions, and health-related quality of life for patients with chronic kidney disease. Ninety eligible patients were enrolled and randomly separated into the exercise group and the control group from November 2015 to May 2016. The exercise group received an individualized exercise program while the control group received only usual care and continued primary lifestyle. Physical function was measured using 6-minute walk test and 10 repetitions of the sit-to-stand test while psychological dimensions were assessed by the Hospital Anxiety and Depression scale and the Self-Efficacy for Exercise scale. Quality of life was evaluated by a disease-specific instrument, the Kidney Disease Quality of Life scale. The differences between the exercise group and the control group were statistically significant for 6-minute walk distance, the time to complete 10 repetitions of the sit-to-stand test, self-efficacy for exercise, anxiety and depression, and all domains of health-related quality of life after a 12-week exercise. This study suggests that home-based individualized exercise program is an effective and feasible way of improving physical function, psychological stress, and health-related quality of life for early stage of chronic kidney disease patients.

Background: Hypertension is highly prevalent among the older adults. Self-care is an effective method for the secondary prevention of hypertension, but until now, there has been no specialized instrument to evaluate the ability for self-care in elderly Chinese patients with hypertension. Objectives: The aims of this study were to cross-culturally translate the Self-care of Hypertension Inventory into Chinese and apply it to elderly patients with preliminary hypertension. Methods: This is a methodological study with steps that included translation, synthesis, back-translation, back-translation review, expert committee review, pretesting, and submission to authors. We conducted preliminary psychometric analyses that included content validity, item-total correlation, internal consistency reliability, principal factor analysis, and test/retest reliability. Results: The translation equivalence was obtained between the adapted version and the original scale. The item-level content validity index had a range of 0.833 to 1. The scale-level content validity average method and Cronbach α were 0.986 and 0.858 for the total scale, respectively. The test/retest reliability was 0.949. Principal factor analyses showed the presence of 4, 1, and 1 latent factors in 3 separate subscales. Conclusions: The Self-care of Hypertension Inventory has been successfully translated and cross-culturally adapted to Chinese. It is suitable for application to elderly Chinese patients with hypertension.