Here we investigate the role of the control of apoptosis in normal cell division. We show that interference with the expression or function of the apoptosis inhibitor survivin causes caspase-dependent cell death in the G2/M phase of the cell cycle, and a cell-division defect characterized by centrosome dysregulation, multipolar mitotic spindles and multinucleated, polyploid cells. Use of a dominant-negative survivin mutant or antisense survivin complementary DNA disrupts a supramolecular assembly of survivin, caspase-3 and the cyclin-dependent-kinase inhibitor p21Waf1/Cip1 within centrosomes, and results in caspase-dependent cleavage of p21. Polyploidy induced by survivin antagonists is accentuated in p21-deficient cells, and corrected by exogenous expression of p21. These findings show that control of apoptosis and preservation of p21 integrity within centrosomes by survivin are required for normal mitotic progression.

Background An important area of research in childhood obesity is the identification of factors that predict or moderate the responses to obesity intervention programs, yet few studies have examined the impact of self-esteem and family functioning on obesity treatment outcomes. Objectives We sought to determine whether baseline self-esteem and family functioning predicted or moderated childhood obesity intervention outcomes at six months. Methods From 2009–2011, seventy-five 10–16 year old, racially/ethnically-diverse obese youths with abnormal glucose tolerance were randomized to six months of an intensive family-based obesity lifestyle intervention (Bright Bodies) or routine outpatient Clinic Care. We examined youth self-esteem/self-concept, parent-rated family functioning, and 6-month outcomes (youths’ glucose tolerance, weight, body mass index, and percent fat). We set the significance threshold as P ≤ 0.05 for moderator and predictor analyses. Results Baseline poor family functioning and self-concept scores indicating high anxiety and low self-esteem predicted poor six-month outcomes overall (Bright Bodies and Clinic Care groups combined). Additionally, baseline self-esteem and family functioning moderated treatment effects–Bright Bodies outperformed Clinic Care in youths with low self-esteem and poorly functioning families, whereas youths with high self-esteem and high-functioning families did similarly well with either intervention. Discussion Our findings suggest intensive family-based lifestyle programs are particularly beneficial for youth with low self-esteem and poorly functioning families. ClinicalTrials.gov Identifier NCT01030978