RNF2/Ring1b negatively regulates p53 expression in selective cancer cell types to promote tumor development

Su, Wenjing; Fang, Junshun; Cheng, Feng; Liu, Chao; Zhou, Fang; Zhang, Jian

doi:10.1073/pnas.1211604110

Cited by 69 publications

(64 citation statements)

References 42 publications

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“…Contrastingly, another polycomb complex protein RNF2, also known as Ring1B/Ring2 is seen to bind with both p53 and MDM2 in colon cancer cell lines and promote MDM2-mediated p53 ubiquitination. RNF2 overexpression also increases the half-life of MDM2 and inhibits its ubiquitination[118],[119]. These observations indicate that polycomb proteins play important roles in p53/MDM2 regulation and may present novel targets for cancer therapy or prevention.…”

Section: Modulators Of the Mdm2-p53 Pathwaymentioning

confidence: 80%

The MDM2-p53 pathway revisited

Nag¹,

Qin²,

et al. 2013

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The p53 tumor suppressor is a key transcription factor regulating cellular pathways such as DNA repair, cell cycle, apoptosis, angiogenesis, and senescence. It acts as an important defense mechanism against cancer onset and progression, and is negatively regulated by interaction with the oncoprotein MDM2. In human cancers, the TP53 gene is frequently mutated or deleted, or the wild-type p53 function is inhibited by high levels of MDM2, leading to downregulation of tumor suppressive p53 pathways. Thus, the inhibition of MDM2-p53 interaction presents an appealing therapeutic strategy for the treatment of cancer. However, recent studies have revealed the MDM2-p53 interaction to be more complex involving multiple levels of regulation by numerous cellular proteins and epigenetic mechanisms, making it imperative to reexamine this intricate interplay from a holistic viewpoint. This review aims to highlight the multifaceted network of molecules regulating the MDM2-p53 axis to better understand the pathway and exploit it for anticancer therapy.

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Section: Modulators Of the Mdm2-p53 Pathwaymentioning

confidence: 80%

The MDM2-p53 pathway revisited

Nag¹,

Qin²,

et al. 2013

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“…However, recently p53 papers discovered a group of E3 ligase or ubiquitin binding proteins, which modulate p53 function in MDM2-dependent manner. Most of these indirect p53 modulators are atypical E3 ubiquitin ligases or harbors ubiquitin binding domain without E3 ligases function [30], [31], [32]. One of the most famous indirect modifiers is MDM4, which shares some common protein domain with MDM2 [33].…”

Section: Discussionmentioning

confidence: 99%

SHARPIN Facilitates p53 Degradation in Breast Cancer Cells

Yang

Wang

et al. 2017

Neoplasia

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The ubiquitin binding protein SHAPRIN is highly expressed in human breast cancer, one of the most frequent female malignancies worldwide. Here, we perform SHARPIN depletion in breast cancer cells together with RNA sequencing. The global expression profiling showed p53 signaling as a potential SHARPIN target. SHARPIN depletion decreased cell proliferation, which effect could be rescue by p53 knocking down. Depletion SHARPIN significantly increases p53 protein level and its target genes in multiple breast cancer cell lines. Further experiment revealed that SHARPIN could facilitate p53 poly-ubiquitination and degradation in MDM2 dependent manner. Immuno-precipitation assay showed that SHARPIN associated with MDM2 and prolonged MDM2 protein stability. Analysis of public available database showed SHARPIN correlated with poor prognosis specifically in p53 wild-type breast cancer patients. Together, our finding revealed a novel modifier for p53/MDM2 complex and suggested SHARPIN as a promising target to restore p53 function in breast cancer.

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“…Another PRC1 core subunit, ring finger protein 2 (RNF2, also known as RING2), has been identified as an E3 ligase that targets p53 for degradation . The E3 ligase activity of RNF2 had already been shown to require BMI1 .…”

Section: Non‐classical‐polycomb Functions Of Pcg Proteinsmentioning

confidence: 99%

Polycomb Group (PcG) Proteins and Human Cancers: Multifaceted Functions and Therapeutic Implications

Wang

Qin

Voruganti

et al. 2015

Medicinal Research Reviews

105

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Polycomb group (PcG) proteins are transcriptional repressors that regulate several crucial developmental and physiological processes in the cell. More recently, they have been found to play important roles in human carcinogenesis and cancer development and progression. The deregulation and dysfunction of PcG proteins often lead to blocking or inappropriate activation of developmental pathways, enhancing cellular proliferation, inhibiting apoptosis, and increasing the cancer stem cell population. Genetic and molecular investigations of PcG proteins have long been focused on their PcG functions. However, PcG proteins have recently been shown to exert non-polycomb functions, contributing to the regulation of diverse cellular functions. We and others have demonstrated that PcG proteins regulate the expression and function of several oncogenes and tumor suppressor genes in a PcG-independent manner, and PcG proteins are associated with the survival of patients with cancer. In this review, we summarize the recent advances in the research on PcG proteins, including both the polycomb-repressive and non-polycomb functions. We specifically focus on the mechanisms by which PcG proteins play roles in cancer initiation, development, and progression. Finally, we discuss the potential value of PcG proteins as molecular biomarkers for the diagnosis and prognosis of cancer, and as molecular targets for cancer therapy.

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RNF2/Ring1b negatively regulates p53 expression in selective cancer cell types to promote tumor development

Cited by 69 publications

References 42 publications

The MDM2-p53 pathway revisited

The MDM2-p53 pathway revisited

SHARPIN Facilitates p53 Degradation in Breast Cancer Cells

Polycomb Group (PcG) Proteins and Human Cancers: Multifaceted Functions and Therapeutic Implications

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