Functional studies of the deubiquitinating enzymes USP19, USP4 and UCH-L1

El marcaje de proteínas con ubiquitina, conocido como ubiquitinación, cumple diferentes funciones que incluyen la regulación de varios procesos celulares, tales como: la degradación de proteínas por medio del proteosoma, la reparación del ADN, la señalización mediada por receptores de membrana, y la endocitosis, entre otras (1). Las moléculas de ubiquitina pueden ser removidas de sus sustratos gracias a la acción de un gran grupo de proteasas, llamadas enzimas deubiquitinizantes (DUBs) (2). Las DUBs son esenciales para la manutención de la homeostasis de la ubiquitina y para la regulación del estado de ubiquitinación de diferentes sustratos. El gran número y la diversidad de DUBs descritas refleja tanto su especificidad como su utilización para regular un amplio espectro de sustratos y vías celulares. Aunque muchas DUBs han sido estudiadas a profundidad, actualmente se desconocen los sustratos y las funciones biológicas de la mayoría de ellas. En este trabajo se investigaron las funciones de las DUBs: USP19, USP4 y UCH-L1. Utilizando varias técnicas de biología molecular y celular se encontró que: i) USP19 es regulada por las ubiquitin ligasas SIAH1 y SIAH2 ii) USP19 es importante para regular HIF-1α, un factor de transcripción clave en la respuesta celular a hipoxia, iii) USP4 interactúa con el proteosoma, iv) La quimera mCherry-UCH-L1 reproduce parcialmente los fenotipos que nuestro grupo ha descrito previamente al usar otros constructos de la misma enzima, y v) UCH-L1 promueve la internalización de la bacteria Yersinia pseudotuberculosis.

Congress composition and electoral advantage

In 2003, an electoral reform changed the mechanism to assign seats in the Colombian Congress. I simulate the 2006 Senate elections using the previous assignment mechanism to determine which senators benefited from the reform, i.e. would have not been elected had the reform not been made. With the results of the simulation, I use a regression discontinuity design to compare the senators that would have been barely elected anyways with those who would have lost, but were near to be elected. I check the differences in the amount of law drafts presented, the attendance to voting sessions, and a discipline index for each senator as proxy of their legislative behavior. I find that the senators benefiting from the reform present a different legislative behavior during the 4-year term with respect to the senators that would have been elected anyways. Since the differential legislative behavior cannot be interpreted as being better (worse) politician, I examine if the behavioral difference gives them an electoral advantage. I find no difference in the electoral result of 2010 Senate election in terms of the probability of being (re)elected in 2010, the share of votes, the share of votes within their party list, and the concentration of their votes. Additionally, I check the probability of being investigated for links with paramilitary groups and I find no differences. The results suggest that political reforms can change the composition of governing or legislative bodies in terms of performance, but it does not necessarily translate into an electoral advantage.