Exploring the role of casein kinase 1α splice variants across cancer cell lines.

Casein kinase 1α (CK1α) is a serine/threonine protein kinase that acts in various cellular processes affecting cell division and signal transduction. CK1α is present as multiple splice variants that are distinguished by the presence or absence of a long insert (L-insert) and a short carboxyl-terminal insert (S-insert). When overexpressed, zebrafish CK1α splice variants exhibit different biological properties, such as subcellular localization and catalytic activity. However, whether endogenous, alternatively spliced CK1α gene products also differ in their biological functions has yet to be elucidated. Here, we identify a panel of splice variant specific CK1α antibodies and use them to show that four CK1α splice variants are expressed in mammals. We subsequently show that the relative abundance of CK1α splice variants varies across distinct mouse tissues and between various cancer cell lines. Furthermore, we identify pathways whose expression is noticeably altered in cell lines enriched with select splice variants of CK1α. Finally, we show that the S-insert of CK1α promotes the growth of HCT 116 cells as cells engineered to lack the S-insert display decreased cell growth. Together, we provide tools and methods to identify individual CK1α splice variants, which we use to begin to uncover the differential biological properties driven by specific splice variants of mammalian CK1α.

Prevalencia de factores de riesgo metabólico en estudiantes universitarios latinoamericanos: una revisión sistemática / Prevalence of metabolic risk factors in Latin American college students: A systematic review

RESUMEN Objetivo Describir la prevalencia de factores de riesgo de tipo metabólico en estudiantes universitarios latinoamericanos a través de una revisión sistemática. Metodología Se realizó una revisión sistemática de artículos en las bases de datos electrónicas de SciELO, PubMed y Google Académico. La búsqueda incluyó referencias publicadas a partir del año 2006 en idiomas español, portugués e inglés que describieran prevalencias de los factores de riesgo mencionados en población universitaria latinoamericana. Resultados Un total de 245 referencias fueron recuperadas, de las cuales 60 fueron seleccionados para su análisis. Los estudiantes universitarios en Latinoamérica presentaron una prevalencia de factores de riesgo metabólicos que, en algunos casos, fue similar a la de la media poblacional en general. Conclusiones Es necesario que la comunidad universitaria y los Gobiernos latinoamericanos planteen estrategias que promuevan estilos de vida saludables tendientes a reducir la adquisición de conductas de riesgo durante la vida universitaria.

ASBTRACT Objective To describe the prevalence of metabolic risk factors in Latin American university students through a systematic review. Methodology A systematic review of articles was carried out in electronic databases SciELO, PubMed and Google Scholar. Search included references, published from 2006 in Spanish, Portuguese, and English, that described the prevalence of risk factors in Latin American college population. Results 245 references were retrieved, of which 60 were selected for analysis. University students in Latin America showed a prevalence of metabolic risk factors that, in some cases, was like that of the population average. Conclusions The university community and Latin American governments must propose strategies to promote healthy lifestyles aimed at reducing the acquisition of risky behaviours during university life.

Casein Kinase 1α as a Regulator of Wnt-Driven Cancer.

Wnt signaling regulates numerous cellular processes during embryonic development and adult tissue homeostasis. Underscoring this physiological importance, deregulation of the Wnt signaling pathway is associated with many disease states, including cancer. Here, we review pivotal regulatory events in the Wnt signaling pathway that drive cancer growth. We then discuss the roles of the established negative Wnt regulator, casein kinase 1α (CK1α), in Wnt signaling. Although the study of CK1α has been ongoing for several decades, the bulk of such research has focused on how it phosphorylates and regulates its various substrates. We focus here on what is known about the mechanisms controlling CK1α, including its putative regulatory proteins and alternative splicing variants. Finally, we describe the discovery and validation of a family of pharmacological CK1α activators capable of inhibiting Wnt pathway activity. One of the important advantages of CK1α activators, relative to other classes of Wnt inhibitors, is their reduced on-target toxicity, overcoming one of the major impediments to developing a clinically relevant Wnt inhibitor. Therefore, we also discuss mechanisms that regulate CK1α steady-state homeostasis, which may contribute to the deregulation of Wnt pathway activity in cancer and underlie the enhanced therapeutic index of CK1α activators.