We previously reported that overexpression of cell division autoantigen 1 (CDA1) in HeLa cells arrests cell growth and inhibits DNA synthesis at S-phase (1). Here we show that CDA1-induced arrest of cell growth is accompanied by increases in protein and mRNA levels of the cyclin-dependent kinase (Cdk) inhibitor protein, p21Waf1/Cip1 (p21). Both p21 induction and cell growth arrest are reversed when CDA1 expression is inhibited. CDA1 also increases p53 protein, but not its mRNA, in a time-and dose-dependent manner. MDM2, a ubiquitin ligase regulating p53 degradation, is inactivated by CDA1, suggesting that p53 protein accumulation is due to decreased protein degradation. Knockdown of p53, using siRNA targeting two sites of p53 mRNA, abrogates transcriptional induction of p21 by CDA1. Deletion of the p53 responsive element in the distal region of p21 promoter attenuates promoter activity in response to CDA1. DNA damage caused by camptothecin treatment increases mRNA and protein levels of CDA1, accompanied by induction of p53. The DNA damage-induced p53 induction is markedly attenuated by CDA1 knockdown. CDA1 induces phosphorylation of ERK1/2(p44/42), an activity blocked by PD98059 and U0126, inhibitors of the upstream kinase MEK1/2. The MEK inhibitors also block induction of p21 mRNA and abrogate p21 promoter activity stimulated by CDA1. Cell cycle kinases, Cdk1, -2, -4, and -6 are inhibited by CDA1 overexpression. We conclude that CDA1 induces p53-and MEK/ERK1/2 MAPK-dependent expression of p21 by acting through the p53 responsive element in the p21 promoter and that this contributes to its antiproliferative activity.

OBJECTIVES:To explore the effects of a discrepancy between actual and preferred living arrangements on the relationship between living arrangements and life satisfaction among the elderly in China.METHODS:Secondary analysis of the 2005 dataset of the Chinese Longitudinal Healthy Longevity Survey was performed. A binary logistic regression model was used to analyze the relationship between life satisfaction and living arrangements.RESULTS:Among those with concordant actual and preferred living arrangements, living in a nursing home increased the likelihood of life satisfaction, whereas living alone and living with a spouse decreased the likelihood of life satisfaction compared to living with the next generation and a spouse. Among those with discordant living arrangements, there were no differences in life satisfaction between the various living arrangements, except that living with a spouse increased life satisfaction compared to living with the next generation and a spouse.CONCLUSIONS:A discrepancy between actual and preferred living arrangements modifies the relationship between life satisfaction and actual living arrangement. Living in a nursing home is a good option for Chinese elder care only if the older individual emotionally accepts it. Living alone or with a spouse is not a good arrangement for elder care, even though it is often preferred by the elderly. Those with discordant living arrangements are more satisfied living with their spouses.

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