RESUMEN
Alcohol Use Disorder (AUD) among older people is under-diagnosed even though the population of older people is rising. Recovery from AUD among older people is a challenging process. A scoping review of the literature on recovery from AUD among older people was conducted to characterize the main topics in recovery. A systematic search was conducted in five databases: Psycinfo, Medline, CINHAL, WoS, and Embase from January 2000 to May 2021 using the PRISMA-ScR. Twenty-five studies met the inclusion criteria. The concept of recovery was defined in 20 studies, where the most frequent term was "abstinence." 16 studies described treatment programs with different types of interventions. Six studies described specific programs for older people; five reported positive outcomes. Future studies should implement a broader definition of recovery that reflects the dimensions of the concept and refers to different age groups, to enable interdisciplinary professionals to develop holistic interventions.
Asunto(s)
Alcoholismo , Humanos , Anciano , Alcoholismo/epidemiologíaRESUMEN
The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin ligase that mediates the proteolysis of cell cycle proteins in mitosis and G(1). We used a yeast three-hybrid screen to identify proteins that interact with the internal ribosome entry site (IRES) of platelet-derived growth factor 2 mRNA. Surprisingly, this screen identified Apc5, although it does not harbor a classical RNA binding domain. We found that Apc5 binds the poly(A) binding protein (PABP), which directly binds the IRES element. PABP was found to enhance IRES-mediated translation, whereas Apc5 overexpression counteracted this effect. In addition to its association with the APC/C complex, Apc5 binds much heavier complexes and cosediments with the ribosomal fraction. In contrast to Apc3, which is associated only with the APC/C and remains intact during differentiation, Apc5 is degraded upon megakaryocytic differentiation in correlation with IRES activation. Expression of Apc5 in differentiated cells abolished IRES activation. This is the first report implying an additional role for an APC/C subunit, apart from its being part of the APC/C complex.
Asunto(s)
Proteínas de Unión a Poli(A)/metabolismo , Biosíntesis de Proteínas , Subunidades de Proteína/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Complejos de Ubiquitina-Proteína Ligasa/metabolismo , Ciclosoma-Complejo Promotor de la Anafase , Animales , Subunidad Apc5 del Ciclosoma-Complejo Promotor de la Anafase , Ciclo Celular/fisiología , Proteínas de Ciclo Celular/metabolismo , Diferenciación Celular/fisiología , Línea Celular , Humanos , Sustancias Macromoleculares , Megacariocitos/citología , Megacariocitos/metabolismo , Factor de Crecimiento Derivado de Plaquetas/genética , Proteínas de Unión a Poli(A)/genética , Subunidades de Proteína/genética , ARN/metabolismo , Ribosomas/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Técnicas del Sistema de Dos Híbridos , Complejos de Ubiquitina-Proteína Ligasa/genéticaRESUMEN
The APC/C(Cdh1) (anaphase promoting complex/cyclosome) targets numerous cell cycle proteins for ubiquitin mediated degradation in late mitosis and G1. The KEN box is one of two major recognition motifs of APC/C(Cdh1) substrates. This motif is however very common and shared by a tenth of the human proteome, the vast majority of which are obviously not APC/C substrates. We have observed that most known functional KEN boxes are followed by a proline residue and show that this proline plays a role in APC/C(Cdh1) specific degradation. This insight can be instrumental for identifying novel APC/C(Cdh1) substrates. We used this KENxP motif to identify human Aurora B and Kid as APC/C(Cdh1) substrates. The degradation of Xenopus XKid at metaphase by APC/C(Cdc20) is essential for chromatid segregation. Human Kid in contrast is degraded later and its APC/C(Cdh1) specific degradation is not required for mitotic progress. It is thus likely that Kid inactivation in G1 takes place both by nuclear sequestration and degradation by the APC/C(Cdh1).
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Cinesinas/metabolismo , Procesamiento Proteico-Postraduccional , Complejos de Ubiquitina-Proteína Ligasa/metabolismo , Secuencias de Aminoácidos , Ciclosoma-Complejo Promotor de la Anafase , Animales , Aurora Quinasa B , Aurora Quinasas , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular , Humanos , Ratones , Prolina/genética , Prolina/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Especificidad por Sustrato , Complejos de Ubiquitina-Proteína Ligasa/genética , Xenopus laevisRESUMEN
The anaphase promoting complex/cyclosome (APC/C), activated by fzy and fzr, degrades cell cycle proteins that carry RXXL or KEN destruction boxes (d-boxes). APC/C substrates regulate sequential events and must be degraded in the correct order during mitosis and G(1). We studied how d-boxes determine APC/C(fzy)/APC/C(fzr) specificity and degradation timing. Cyclin B1 has an RXXL box and is degraded by both APC/C(fzy) and APC/C(fzr); fzy has a KEN box and is degraded by APC/C(fzr) only. We characterized the degradation of substrates with swapped d-boxes. Cyclin B1 with KEN was degraded by APC/C(fzr) only. Fzy with RXXL could be degraded by APC/C(fzy) and APC/C(fzr). Interestingly, APC/C(fzy)- but not APC/C(fzr)-specific degradation is highly dependent on the location of RXXL. We studied degradation of tagged substrates in real time and observed that APC/C(fzr) is activated in early G(1). These observations demonstrate how d-box specificities of APC/C(fzy) and APC/C(fzr), and the successive activation of APC/C by fzy and fzr, establish the temporal degradation pattern. Our observations can explain further why some endogenous RXXL substrates are degraded by APC/C(fzy), while others are restricted to APC/C(fzr).