ABSTRACT
Members of the p53 family of transcription factors-p53, p63, and p73-share a high degree of homology; however, members can be activated in response to different stimuli, perform distinct (sometimes opposing) roles and are expressed in different tissues. The level of complexity is increased further by the transcription of multiple isoforms of each homolog, which may interact or interfere with each other and can impact cellular outcome. Proteins perform their functions through interacting with other proteins (and/or with nucleic acids). Therefore, identification of the interactors of a protein and how they interact in 3D is essential to fully comprehend their roles. By utilizing an in silico protein-protein interaction prediction method-HMI-PRED-we predicted interaction partners of p53 family members and modeled 3D structures of these protein interaction complexes. This method recovered experimentally known interactions while identifying many novel candidate partners. We analyzed the similarities and differences observed among the interaction partners to elucidate distinct functions of p53 family members and provide examples of how this information may yield mechanistic insight to explain their overlapping versus distinct/opposing outcomes in certain contexts. While some interaction partners are common to p53, p63, and p73, the majority are unique to each member. Nevertheless, most of the enriched pathways associated with these partners are common to all members, indicating that the members target the same biological pathways but through unique mediators. p63 and p73 have more common enriched pathways compared to p53, supporting their similar developmental roles in different tissues.
Subject(s)
Transcription Factors , Tumor Suppressor Protein p53 , DNA-Binding Proteins/metabolism , Humans , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Transcription Factors/metabolism , Tumor Protein p73/genetics , Tumor Protein p73/metabolism , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolismSubject(s)
Cell Cycle Proteins/metabolism , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic/immunology , Melanoma/genetics , Skin Neoplasms/genetics , Transcription Factors/metabolism , Cell Cycle Proteins/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Movement/immunology , Gene Knockdown Techniques , Humans , Macrophages/immunology , Melanoma/immunology , Melanoma/pathology , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/immunology , Phagocytosis/genetics , Phagocytosis/immunology , Skin Neoplasms/immunology , Skin Neoplasms/pathology , Transcription Factors/geneticsABSTRACT
Se revisaron 20 pacientes con vejiga neurogénica de alto riesgo sometidos a enterocistoplastia. En 16 pacientes (80 por ciento) se realizó aumento vesical con colon sigmoideo, en tres (15 por ciento) con íleo y en uno (5 por ciento) con uréter. Todos experimentaban deterioro preoperatorio de las vías urinarias superiores, que en siete (35 por ciento) mejoró y en 13 (65 por ciento) se estabilizó, y en ninguno progresó. Tenían reflujo 16 pacientes (80 por ciento), que pudo curarse en 15 (94 por ciento). Otros 15 pacientes (80 por ciento) tenían incontinencia urinaria, y actualmente se conservan secos durante periodos de 31/2 a 4 horas. Los estudios cistométricos indicaron mejoría de 300 por ciento en la capacidad vesical, y disminución de 50 por ciento de la presión vesical. La función renal se estabilizó o mejoró en todos los pacientes. Se presentaron complicaciones sólo en cinco casos (20 por ciento), en dos por suboclusión intestinal, en otros dos por infección de vías urinarias sintomática y en uno por litiasis vesical. Estos resultados corroboran que la enterocistoplastia es la mejor opción de tratamiento en vejigas de alto riesgo y deterioro de vías urinarias superiores
