Proteasome-independent p53 degradation

Nuaaman, Mais M; Benchimol, Samuel

doi:10.1038/cr.2013.38

Cited by 4 publications

(2 citation statements)

References 12 publications

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“…Recent studies show that Diexf homologs in S. cerevisiae (Utp25p) and A. thaliana (Nof1) are nucleolus-localized components of small subunit processome that regulate pre-rRNA processing [ 16 , 18 , 28 ]. In addition to this function, Def also negatively regulates p53 activity in zebrafish via proteasome-independent degradation of p53 protein in the nucleolus [ 15 , 17 , 29 ]. Here, we first highlighted a significant mutually exclusive relationship between DIEXF amplification and TP53 mutation in human breast cancers.…”

Section: Discussionmentioning

confidence: 99%

Loss of digestive organ expansion factor (Diexf) reveals an essential role during murine embryonic development that is independent of p53

et al. 2017

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Increased levels of inhibitors of the p53 tumor suppressor such as Mdm2 and Mdm4 drive tumor development and thus serve as targets for therapeutic intervention. Recently, digestive organ expansion factor (Diexf) has been identified as a novel inhibitor of p53 in zebrafish. Here, we address the potential role of Diexf as a regulator of the p53 pathway in mammals by generating Diexf knockout mice. We demonstrate that, similar to Mdm2 and Mdm4, homozygous deletion of Diexf is embryonic lethal. However, unlike in Mdm2 and Mdm4 mice, loss of p53 does not rescue this phenotype. Moreover, Diexf heterozygous animals are not sensitive to sub-lethal ionizing radiation. Thus, we conclude that Diexf is an essential developmental gene in the mouse, but is not a significant regulator of the p53 pathway during development or in response to ionizing radiation.

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Section: Discussionmentioning

confidence: 99%

Loss of digestive organ expansion factor (Diexf) reveals an essential role during murine embryonic development that is independent of p53

et al. 2017

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“…Kimutatták, hogy a Kalpain 3 cisztein proteáz, komplexet képezve a DEF fehérjével, részt vesz a P53 lebontásában. Ezekből az eredményekből arra lehet következtetni, hogy a DEF egy "Scaffold" fehérjeként, a Kalpain 3 proteázzal alkotott kölcsönhatásán keresztül részt vesz a nukleáris P53 fehérje szint szabályozásában (124,125). …”

Section: A P53 Proteoszómális éS Proteoszóma-független Bontásaunclassified

A humán P53 fehérje transzkripció elongációban betöltött, eddig nem azonosított szerepének jellemzése

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Mutations in the TP53 gene affected recruitment of 53BP1 protein to DNA lesions, but level of 53BP1 was stable after γ-irradiation that depleted MDC1 protein in specific TP53 mutants

Suchánková

Legartová

Růčková

et al. 2017

Histochem Cell Biol

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53BP1 is a very well-known protein that is recruited to DNA lesions. The focal accumulation of p53 binding protein, 53BP1, is a main feature indicating the repair of spontaneous or irradiation-induced foci (IRIF). Thus, here, we addressed the question of whether mutations in the TP53 gene, which often affect the level of p53 protein, can change the recruitment of 53BP1 to γ- or UVA-irradiated chromatin. In various TP53 mutants, we observed a distinct accumulation of 53BP1 protein to UV-induced DNA lesions: in R273C mutants, 53BP1 appeared transiently at DNA lesions, during 10-30 min after irradiation; the mutation R282W was responsible for accumulation of 53BP1 immediately after UVA-damage; and in L194F mutants, the first appearance of 53BP1 protein at the lesions occurred during 60-70 min. These results showed that specific mutations in the TP53 gene stand behind not only different levels of p53 protein, but also affect the localized kinetics of 53BP1 protein in UVA-damaged chromatin. However, after γ-irradiation, only G245S mutation in TP53 gene was associated with surprisingly decreased level of 53BP1 protein. In other mutant cell lines, levels of 53BP1 were not affected by γ-rays. To these effects, we conversely found a distinct number of 53BP1-positive irradiation-induced foci in various TP53 mutants. The R280K, G245S, L194F mutations, or TP53 deletion were also characterized by radiation-induced depletion in MDC1 protein. Moreover, in mutant cells, an interaction between MDC1 and 53BP1 proteins was abrogated when compared with wild-type counterpart. Together, the kinetics of 53BP1 accumulation at UV-induced DNA lesions is different in various TP53 mutant cells. After γ-irradiation, despite changes in a number and a volume of 53BP1-positive foci, levels of 53BP1 protein were relatively stable. Here, we showed a link between the status of MDC1 protein and TP53 gene, which specific mutations caused radiation-induced MDC1 down-regulation. This observation is significant, especially with regard to radiotherapy of tumors with abrogated function of TP53 gene.

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Proteasome-independent p53 degradation

Cited by 4 publications

References 12 publications

Loss of digestive organ expansion factor (Diexf) reveals an essential role during murine embryonic development that is independent of p53

Loss of digestive organ expansion factor (Diexf) reveals an essential role during murine embryonic development that is independent of p53

A humán P53 fehérje transzkripció elongációban betöltött, eddig nem azonosított szerepének jellemzése

Mutations in the TP53 gene affected recruitment of 53BP1 protein to DNA lesions, but level of 53BP1 was stable after γ-irradiation that depleted MDC1 protein in specific TP53 mutants

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