The SWIB/MDM2 motif of UBE4B activates the p53 pathway

Wu, Hong; Leng, Sarah; Abuetabh, Yasser; Sergi, Consolato; Eisenstat, David D.; Leng, Roger

doi:10.1016/j.omtn.2023.02.002

Cited by 3 publications

(3 citation statements)

References 65 publications

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“…We identified that PRMT1 is a sharing substrate by CHIP and E4B [28]. It has been reported that the U‐box domain is an essential part of E4B by verifying the self‐ubiquitination of E4B, and the activity of U‐box domain is closely related to the integrity of its amino acid sequence and spatial structure [41,42]. The activity of E4B can be enhanced by modifying certain amino acid sequences in its U‐box domain that enhances its affinity for E2 [23].…”

Section: Discussionmentioning

confidence: 99%

Recruitment of ubiquitin E2 enzymes is determined jointly by the U‐box domains and substrates of E3 ligases

Jin,

Li,

et al. 2024

FEBS Letters

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Ubiquitination is a cascade reaction involving E1, E2, and E3 enzymes. The orthogonal ubiquitin transfer (OUT) method has been previously established to identify potential substrates of E3 ligases. In this study, we verified the ubiquitination of five substrates mediated by the E3 ligases CHIP and E4B. To further explore the activity of U‐box domains of E3 ligases, two mutants with the U‐box domains interchanged between CHIP and E4B were generated. They exhibited a significantly reduced ubiquitination ability. Additionally, different E3s recruited similar E2 ubiquitin‐conjugating enzymes when ubiquitinating the same substrates, highlighting that U‐box domains determined the E2 recruitment, while the substrate determined the E2 selectivity. This study reveals the influence of substrates and U‐box domains on E2 recruitment, providing a novel perspective on the function of U‐box domains of E3 ligases.

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Section: Discussionmentioning

confidence: 99%

Recruitment of ubiquitin E2 enzymes is determined jointly by the U‐box domains and substrates of E3 ligases

Jin,

Li,

et al. 2024

FEBS Letters

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“…The expression of p53 and Bax proteins was also reduced by C646. p53 is a transcription factor capable of activating the apoptotic pathway by upregulating pro-apoptotic proteins like Bax [ 35 ]. A prior study reported that p53 deficiency reduced the number of apoptotic hepatocytes and mitigated NASH progression in MCD diet-fed mice [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological inhibition of p300 ameliorates steatosis, inflammation, and fibrosis in mice with non-alcoholic steatohepatitis

Kim,

Yang,

Kim

et al. 2024

Heliyon

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“…Combined normal P53 and MDM2 expression secures cell cycle stability and functionality, partially under the influence of ubiquitin ligases ( 23 ). In neoplastic, pre- and malignant tissues this balance is aborted, leading to excessive cell proliferation.…”

Section: P53/mdm2 Alterations In Colon Adenocarcinomamentioning

confidence: 99%

P53/MDM2 Complex-Based Targeted Strategies in Colon Adenocarcinoma

Niotis

Tsiambas

Dimitroulis

et al. 2023

ama

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In the current molecular review, we describe the mechanisms of TP53/MDM2 deregulation and their impact on the colon adenocarcinoma molecular substrate and phenotype. Among the genes that are critically altered in carcinogenesis, the TP53 tumor suppressor gene is of major importance. The TP53 gene (gene locus: 17p13.1) regulates the cell cycle by controlling the G1/S and G2/M checkpoints securing the normal sequence of cell cycle phases. Furthermore, it is involved in apoptosis programmed cell death. The gene is mutated or epigenetically altered in all epithelial malignancies, including colon adenocarcinoma. Additionally, Mouse Double Minute 2 Homolog (MDM2), a proto-oncogene (12q14.3), acts as a major negative regulator for p53 expression in the p53-MDM2 auto-regulatory pathway. MDM2 binds directly to p53 and represses its transcriptional activity, promoting p53 degradation.Conclusion. In colon adenocarcinoma, MDM2 oncogene overexpression directly influences p53 oncoprotein expression levels.

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The SWIB/MDM2 motif of UBE4B activates the p53 pathway

Cited by 3 publications

References 65 publications

Recruitment of ubiquitin E2 enzymes is determined jointly by the U‐box domains and substrates of E3 ligases

Recruitment of ubiquitin E2 enzymes is determined jointly by the U‐box domains and substrates of E3 ligases

Pharmacological inhibition of p300 ameliorates steatosis, inflammation, and fibrosis in mice with non-alcoholic steatohepatitis

P53/MDM2 Complex-Based Targeted Strategies in Colon Adenocarcinoma

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