RESUMO
PES1 is a component of the PeBoW complex, which is required for the maturation of 28S and 5.8S ribosomal RNAs, as well as for the formation of the 60S ribosome. Deregulation of ribosomal biogenesis can contribute to carcinogenesis. In this study, we showed that PES1 could be modified by the small ubiquitin-like modifier (SUMO) SUMO-1, SUMO-2 and SUMO-3, and SUMOylation of PES1 was stimulated by estrogen (E2). One major SUMOylation site (K517) was identified in the C-terminal Glu-rich domain of PES1. Substitution of K517 with arginine abolished the SUMOylation of PES1. SUMOylation also stabilized PES1 through inhibiting its ubiquitination. In addition, PES1 SUMOylation positively regulated the estrogen signaling pathway. SUMOylation enhanced the ability of PES1 to promote estrogen receptor α (ERα)-mediated transcription by increasing the stability of ERα, both in the presence and absence of E2. Moreover, SUMOylation of PES1 also increased the proportion of S-phase cells in the cell cycle and promoted the proliferation of breast cancer cells both in vitro and in vivo. These findings showed that posttranslational modification of PES1 by SUMOylation may serve as a key factor that regulates the function of PES1 in vivo.
Assuntos
Proteínas/metabolismo , Sumoilação , Ubiquitinação , Animais , Neoplasias da Mama/metabolismo , Células COS , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Chlorocebus aethiops , Receptor alfa de Estrogênio , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Complexo de Endopeptidases do Proteassoma/metabolismo , Processamento de Proteína Pós-Traducional , RNA Ribossômico 28S/metabolismo , RNA Ribossômico 5,8S/metabolismo , Proteínas de Ligação a RNA , Ativação TranscricionalRESUMO
We attempted to systematically determine the association between dietary intake of vitamin C and risk of prostate cancer. PubMed and Embase were searched to obtain eligible studies published before February 2015. Cohort or case-control studies that reported the relative risk (RR)/odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between vitamin C intake and prostate cancer risk were included. Eighteen studies regarding dietary vitamin C intake were finally obtained, with a total of 103,658 subjects. The pooled RR of prostate cancer for the highest versus the lowest categories of dietary vitamin C intake was 0.89 (95%CI: 0.83-0.94; p = 0.000) with evidence of a moderate heterogeneity (I(2) = 39.4%, p = 0.045). Meta-regression analysis suggested that study design accounted for a major proportion of the heterogeneity. Stratifying the overall study according to study design yielded pooled RRs of 0.92 (95%CI: 0.86-0.99, p = 0.027) among cohort studies and 0.80 (95%CI: 0.71-0.89, p = 0.000) among case-control studies, with no heterogeneity in either subgroup. In the dose-response analysis, an inverse linear relationship between dietary vitamin C intake and prostate cancer risk was established, with a 150 mg/day dietary vitamin C intake conferred RRs of 0.91 (95%CI: 0.84-0.98, p = 0.018) in the overall studies, 0.95 (95%CI: 0.90-0.99, p = 0.039) in cohort studies, and 0.79 (95%CI: 0.69-0.91, p = 0.001) in case-control studies. In conclusion, intake of vitamin C from food was inversely associated with prostate cancer risk in this meta-analysis.
