Loss of p53 enhances the function of the endoplasmic reticulum through activation of the IRE1α/XBP1 pathway

Altered regulation of ER stress response has been implicated in a variety of human diseases, such as cancer and metabolic diseases. Excessive ER function contributes to malignant phenotypes, such as chemoresistance and metastasis. Here we report that the tumor suppressor p53 regulates ER function in response to stress. We found that loss of p53 function activates the IRE1α/XBP1 pathway to enhance protein folding and secretion through upregulation of IRE1α and subsequent activation of its target XBP1. We also show that wild-type p53 interacts with synoviolin (SYVN1)/HRD1/DER3, a transmembrane E3 ubiquitin ligase localized to ER during ER stress and removes unfolded proteins by reversing transport to the cytosol from the ER, and its interaction stimulates IRE1α degradation. Moreover, IRE1α inhibitor suppressed protein secretion, induced cell death in p53-deficient cells, and strongly suppressed the formation of tumors by p53-deficient human tumor cells in vivo compared with those that expressed wild-type p53. Therefore, our data imply that the IRE1α/XBP1 pathway serves as a target for therapy of chemoresistant tumors that express mutant p53

CDIP1-BAP31 Complex Transduces Apoptotic Signals from Endoplasmic Reticulum to Mitochondria under Endoplasmic Reticulum Stress

SummaryResolved endoplasmic reticulum (ER) stress response is essential for intracellular homeostatic balance, but unsettled ER stress can lead to apoptosis. Here, we show that a proapoptotic p53 target, CDIP1, acts as a key signal transducer of ER-stress-mediated apoptosis. We identify B-cell-receptor-associated protein 31 (BAP31) as an interacting partner of CDIP1. Upon ER stress, CDIP1 is induced and enhances an association with BAP31 at the ER membrane. We also show that CDIP1 binding to BAP31 is required for BAP31 cleavage upon ER stress and for BAP31-Bcl-2 association. The recruitment of Bcl-2 to the BAP31-CDIP1 complex, as well as CDIP1-dependent truncated Bid (tBid) and caspase-8 activation, contributes to BAX oligomerization. Genetic knockout of CDIP1 in mice leads to impaired response to ER-stress-mediated apoptosis. Altogether, our data demonstrate that the CDIP1/BAP31-mediated regulation of mitochondrial apoptosis pathway represents a mechanism for establishing an ER-mitochondrial crosstalk for ER-stress-mediated apoptosis signaling

Motivação de gestantes para o aleitamento materno Motivating breastfeeding among expectant mothers

OBJETIVO: Conhecer os motivos de gestantes para o aleitamento materno. MÉTODOS: É um estudo qualitativo realizado com 164 gestantes assistidas no pré-natal em dois Centros de Saúde na região central da cidade de São Paulo. Os dados foram coletados por meio de entrevistas semi-estruturadas sobre motivação para amamentar. As narrativas foram organizadas em planilha eletrônica em busca de categorias. RESULTADOS: As principais categorias identificadas estavam relacionadas à saúde da criança, da mulher e aos benefícios da prática de amamentar e do leite materno. A maioria das mulheres (98,8%) foi favorável à amamentação. Benefícios à saúde da criança foi o motivo mais freqüente (73,8%). CONCLUSÃO: A motivação ao aleitamento materno foi centrada nos benefícios à saúde da criança. A amamentação é valorizada independentemente da vontade materna.<br>OBJECTIVE: The present study sought to discover the reasons for expectant mothers to breastfeed. METHODS: This was a qualitative study involving 164 expectant mothers attending prenatal care in two health centers of the city of São Paulo. Semi-structured interviews were done to collect data on the reasons to breastfeed. The information was organized in a spreadsheet to search for categories. RESULTS: The main identified categories regarded the child's and woman's health and the benefits of breastfeeding and breast milk. The majority of the women (98.8%) regarded breastfeeding favorably. Benefit to the child's health was the reason mentioned most often (73.8%). CONCLUSION: Motivation to breastfeed was based on benefits to the child's health. Breastfeeding is valued regardless of the mother's will

Influência das avós na alimentação de lactentes: o que dizem suas filhas e noras Influencia de las abuelas en la alimentación de lactantes Influence of grandmothers on infant feeding: what they say to their daughters and granddaughters

OBJETIVO: Identificar as práticas de primíparas sobre a alimentação de crianças lactentes aprendidas com a mãe e/ou sogra. MÉTODOS: Trata-se de pesquisa qualitativa, do tipo descritiva. Os sujeitos foram 11 primíparas, usuárias do Sistema Único de Saúde de Palmeira das Missões/RS. Os dados foram coletados por entrevista semiestruturada e analisados por meio da análise temática. RESULTADOS: Emergiram três temas: práticas de alimentação transmitidas pelas avós; influência das avós na alimentação do lactente; sentimentos das primíparas em relação às ações das avós relativas à alimentação do lactente. CONCLUSÕES: As avós são importantes no que diz respeito à transmissão de conhecimentos, saberes e experiências relativas à alimentação do lactente. Para que a assistência de enfermagem priviligie a autonomia dos sujeitos que envolve corresponsabilidade e congruência cultural, o enfermeiro deve considerar as interações do grupo familiar que, em seu movimento dialético, modulam e são moduladas pela cultura.<br>OBJETIVO: Identificar las prácticas de primigestas sobre la alimentación de niños lactantes aprendidas con la madre y/o suegra. MÉTODOS: Se trata de una investigación cualitativa, de tipo descriptiva. Los sujetos fueron 11 primigestas, usuarias del Sistema Único de Salud de Palmeira das Missões/RS. Los datos fueron recolectados por entrevista semiestructurada y analizados por medio del análisis temático. RESULTADOS: Emergieron tres temas: prácticas de alimentación transmitidas por las abuelas; influencia de las abuelas en la alimentación del lactante; sentimientos de las primigestas en relación a las acciones de las abuelas relativas a la alimentación del lactante. CONCLUSIONES: Las abuelas son importantes en lo referente a la transmisión de conocimientos, saberes y experiencias relativas a la alimentación del lactante. Para que la asistencia de enfermería privilegie la autonomía de los sujetos que involucra corresponsabilidad y congruencia cultural, el enfermero debe considerar las interacciones del grupo familiar que, en su movimiento dialéctico, modulan y son moduladas por la cultura.<br>OBJECTIVE: To identify practices of primiparas about infant feeding of infants learned from the mother and/or grandmother. METHODS: This was a qualitative, descriptive research study. The subjects were 11 primiparas, who used the Unified Health System of Palmeira das Missões/ RS. Data were collected through semi-structured interviews and analyzed using thematic analysis. RESULTS: Three themes emerged: practices of infant feeding transmitted by grandmothers; influence of grandmothers on infant feeding; feelings of primiparas in regard to the actions of grandmothers on infant feeding. CONCLUSIONS: The grandmothers are important with regard to the transmission of knowledge, wisdom and experiences related to infant feeding. For nursing care focused on the subjects' autonomy and responsibility that involves cultural congruence, the nurse should consider that the interactions of the family group, in its dialectical movement, modulate and are modulated by their culture