Tumor suppressor p53 has a key role in maintaining genomic stability and preventing tumorigenesis through its regulation of cellular stress responses, including apoptosis, cell cycle arrest and senescence. To ensure its proper levels and functions in cells, p53 is tightly regulated mainly through post-translational modifications, such as ubiquitination. Here, we identified E3 ubiquitin ligase TRIM32 as a novel p53 target gene and negative regulator to regulate p53-mediated stress responses. In response to stress, such as DNA damage, p53 binds to the p53 responsive element in the promoter of the TRIM32 gene and transcriptionally induces the expression of TRIM32 in cells. In turn, TRIM32 interacts with p53 and promotes p53 degradation through ubiquitination. Thus, TRIM32 negatively regulates p53-mediated apoptosis, cell cycle arrest and senescence in response to stress. TRIM32 is frequently overexpressed in different types of human tumors. TRIM32 overexpression promotes cell oncogenic transformation and tumorigenesis in mice in a largely p53-dependent manner. Taken together, our results demonstrated that as a novel p53 target and a novel negative regulator for p53, TRIM32 has an important role in regulation of p53 and p53-mediated cellular stress responses. Furthermore, our results also revealed that impairing p53 function is a novel mechanism for TRIM32 in tumorigenesis.
ABSTRACT. The aim of this study was to compare the proteomics pattern of the kidneys from Cyld knockout mice with that from normal mouse kidneys and establish a preliminary understanding of the role of Cyld in the kidney. Proteins from the kidneys of knockout Cyld mice and wild-type mice were extracted, isobaric tags for relative and absolute quantitation (iTRAQ) was performed, and the proteomics patterns of the two groups were compared. The genotypes of the mice were verified by polymerase chain reaction. A total of 1748 proteins with a local false discovery rate of ≤5% were identified, among which 1437 proteins were reliably recognized and quantified. The expression of two dysregulated proteins was confirmed by Western blotting. Gene ontology and pathway analyses indicated that the proteins identified were involved in biological processes, cell components, and molecular functions, and participated in different pathways. Some of the proteins identified were relevant to renal function or kidney diseases. The difference between the proteomics profiles of kidneys from Cyld knockout mice and wild-type mice was prominent, which correlates to kidney dysfunction and the development of renal diseases.
The ferroelectric thin films of bismuth titanate (Bi4Ti3O12) have been prepared by metalorganic chemical vapor deposition ( MOCVD) technique at atmosphere. The triphenyl bismuth (Bi(CaH5 ) 3)and tetrabutyl titanate (C16H36O4Ti) were used as precursors. Dense Bi4Ti3 O12 films with smooth shinning surface have been grown on Si( 100) substrates at 550°C whithout postannealing. The as- grown films were characterized by X-ray diffraction analysis (XRD), scanning electron microscopy (SEM) and energy dispersion analysis ( EDAX). The films showed well-ordered crystallinity with an (001)preffered orientation. The influence of growth parameters on deposition rate, composition and morphology of as-grown films was also discussed.
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