Phosphorylation of Kif26b Promotes Its Polyubiquitination and Subsequent Proteasomal Degradation during Kidney Development

Kif26b, a member of the kinesin superfamily proteins (KIFs), is essential for kidney development. Kif26b expression is restricted to the metanephric mesenchyme, and its transcription is regulated by a zinc finger transcriptional regulator Sall1. However, the mechanism(s) by which Kif26b protein is regulated remain unknown. Here, we demonstrate phosphorylation and subsequent polyubiquitination of Kif26b in the developing kidney. We find that Kif26b interacts with an E3 ubiquitin ligase, neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) in developing kidney. Phosphorylation of Kif26b at Thr-1859 and Ser-1962 by the cyclin-dependent kinases (CDKs) enhances the interaction of Kif26b with Nedd4. Nedd4 polyubiquitinates Kif26b and thereby promotes degradation of Kif26b via the ubiquitin-proteasome pathway. Furthermore, Kif26b lacks ATPase activity but does associate with microtubules. Nocodazole treatment not only disrupts the localization of Kif26b to microtubules but also promotes phosphorylation and polyubiquitination of Kif26b. These results suggest that the function of Kif26b is microtubule-based and that Kif26b degradation in the metanephric mesenchyme via the ubiquitin-proteasome pathway may be important for proper kidney development

Asociación de los tipos de carencia y grado de desarrollo humano con la mortalidad infantil en México, 2008 Association between types of need, human development index, and infant mortality in Mexico, 2008

El objetivo del artículo fue conocer la asociación entre los diferentes tipos de carencia social y económica y los niveles de mortalidad infantil reportados durante el 2008 en México. Se realizó un estudio ecológico, analizando la correlación y el riesgo relativo entre el índice de desarrollo humano y distintos niveles de carencias sociales y económicas con las tasas de mortalidad infantil reportadas a nivel nacional y estatal. Existe una fuerte correlación entre un mayor nivel de desarrollo humano con una menor tasa de mortalidad. La carencia educativa y el atraso en la calidad y espacio de la vivienda se asocian con una mayor tasa de mortalidad infantil. Si bien la mortalidad infantil en México ha disminuido notablemente en los últimos 28 años, su reducción no ha sido homogénea y se mantienen inequidades que determinan las tasas de mortalidad en relación a los niveles diferenciados de pobreza. Es necesario el diseño de programas con una visión transdisciplinaria que permitan disminuir las tasas de mortalidad con el pleno desarrollo de los individuos y sus familias<br>The aim of this study was to assess the association between different types of economic and social deprivation and infant mortality rates reported in 2008 in Mexico. We conducted an ecological study analyzing the correlation and relative risk between the human development index and levels of social and economic differences in State and national infant mortality rates. There was a strong correlation between higher human development and lower infant mortality. Low schooling and poor housing and crowding were associated with higher infant mortality. Although infant mortality has declined dramatically in Mexico over the last 28 years, the decrease has not been homogeneous, and there are persistent inequalities that determine mortality rates in relation to different poverty levels. Programs with a multidisciplinary approach are needed to decrease infant mortality rates through comprehensive individual and family development