Degradation of Hof1 by SCF(Grr1) is important for actomyosin contraction during cytokinesis in yeast

SCF-type (SCF: Skp1–Cullin–F-box protein complex) E3 ligases regulate ubiquitin-dependent degradation of many cell cycle regulators, mainly at the G1/S transition. Here, we show that SCF(Grr1) functions during cytokinesis by degrading the PCH protein Hof1. While Hof1 is required early in mitosis to assemble a functional actomyosin ring, it is specifically degraded late in mitosis and remains unstable during the entire G1 phase of the cell cycle. Degradation of Hof1 depends on its PEST motif and a functional 26S proteasome. Interestingly, degradation of Hof1 is independent of APC(Cdh1), but instead requires the SCF(Grr1) E3 ligase. Grr1 is recruited to the mother–bud neck region after activation of the mitotic-exit network, and interacts with Hof1 in a PEST motif-dependent manner. Our results also show that downregulation of Hof1 at the end of mitosis is necessary to allow efficient contraction of the actomyosin ring and cell separation during cytokinesis. SCF(Grr1)-mediated degradation of Hof1 may thus represent a novel mechanism to couple exit from mitosis with initiation of cytokinesis

Successful Cognitive Aging and Health-Related Quality of Life in Younger and Older Adults Infected with HIV

OBJECTIVE: Neurocognitive impairments commonly occur and adversely impact everyday functioning in older adults infected with HIV, but little is known about successful cognitive aging (SCA) and its health-related quality of life (HRQoL) correlates. METHOD: Seventy younger (≤ 40 years) and 107 older (≥ 50 years) HIV+ adults, as well as age-matched seronegative comparison groups of younger (N=48) and older (N=77) subjects completed a comprehensive battery of neuropsychological, psychiatric, medical, and HRQoL assessments. SCA was operationalized as the absence of both performance-based neurocognitive deficits and self-reported symptoms (SCA-ANDS) as determined by published normative standards. RESULTS: A stair-step decline in SCA-ANDS was observed in accordance with increasing age and HIV serostatus, with the lowest rates of SCA-ANDS found in the older HIV+ group (19%). In both younger and older HIV+ adults, SCA-ANDS was strongly related to better mental HRQoL. CONCLUSION: HIV infection has additive adverse effects on SCA, which may play a unique role in mental well-being among HIV-infected persons across the lifespan