Chaperoning of Mutant p53 Protein by Wild-type p53 Protein Causes Hypoxic Tumor Regression

Gogna, Rajan; Madan, Esha; Kuppusamy, Periannan; Pati, Uttam

doi:10.1074/jbc.m111.317354

Cited by 31 publications

(61 citation statements)

References 34 publications

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“…Several clinical trials have been based on strategies to reintroduce wildtype P53 copies into cancerous tissues (27)(28)(29). In addition, there have been several clinical attempts to use molecular chaperones that can rescue wildtype P53 (30)(31)(32)(33). Because of the oncogenic role of mutant P53 (3,26), reactivation of transcriptionally inactive mutant P53 is a promising approach to cancer therapy (30).…”

Section: P53mentioning

confidence: 99%

The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53

Madan

Parker

Bauer

et al. 2018

Journal of Biological Chemistry

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Section: P53mentioning

confidence: 99%

The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53

Madan

Parker

Bauer

et al. 2018

Journal of Biological Chemistry

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“…For hypoxic exposure, cells were placed into a humidified chamber maintained at 1.8% O 2 and 5% CO 2 (balance N 2 ) for 24 h, as described previously (18,19,21). The oxygen level in the chamber was monitored with an oxygen analyzer (Vascular Technology).…”

Section: Cell Lines and Culture Conditions Kb Mcf-7 Hct P53mentioning

confidence: 99%

“…p53 cDNA, SCO2 cDNA, p53 small interfering RNA (siRNA), and SCO2 siRNA were purchased from Origene (18,19,(21)(22)(23)(24)(25). Cells were split 2 days before transfection at a density of 5 ϫ 10 5 cells per plate.…”

Section: Cell Lines and Culture Conditions Kb Mcf-7 Hct P53mentioning

confidence: 99%

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SCO2 Induces p53-Mediated Apoptosis by Thr⁸⁴⁵ Phosphorylation of ASK-1 and Dissociation of the ASK-1–Trx Complex

Madan

Gogna

Kuppusamy

et al. 2013

Molecular and Cellular Biology

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“…Hypoxia-induced p53 fails to transactivate its target genes (55). Wild-type p53 has been shown to function as a molecular chaperone and to rescue mutant p53 in hypoxic tumors and subsequently cause tumor regression (56). There are multiple contradictory reports on reciprocal interaction of p53 with hypoxic signaling (39,54,(57)(58)(59)(60).…”

Section: Discussionmentioning

confidence: 99%

Tip110 Regulates the Cross Talk between p53 and Hypoxia-Inducible Factor 1α under Hypoxia and Promotes Survival of Cancer Cells

Timani

Liu

Fan

et al. 2015

Molecular and Cellular Biology

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bHypoxia often occurs under various physiological and pathophysiological conditions, including solid tumors; it is linked to malignant transformation, metastatic progression, and treatment failure or resistance. Tip110 protein plays important roles in several known physiological and pathophysiological processes, including cancers. Thus, in the present study we investigated the regulation of Tip110 expression under hypoxia. Hypoxia led to Tip110 protein degradation through the ubiquitin-proteasome system. Under hypoxia, Tip110 stabilized p53, which in return destabilized Tip110. In addition, Tip110 regulated hypoxia-inducible factor 1␣ (HIF-1␣), likely through enhancement of its protein stability. Furthermore, Tip110 upregulated p300, a known coactivator for both p53 and HIF-1␣. Expression of a p53(22/23) mutant deficient in p300 binding accelerated Tip110 degradation under hypoxia. Tip110 knockdown resulted in the inhibition of cell proliferation and cell death in the presence of p53. Finally, significantly less Tip110, p53, and HIF-1␣ was detected in the hypoxic region of bone metastasis tumors in a mouse model of human melanoma cells. Taken together, these results suggest Tip110 is an important mediator in the cross talk between p53 and HIF-1␣ in response to hypoxic stress. Hypoxia is the common characteristic of many solid tumors. The adaptation of cells to hypoxia is mediated by hypoxiainducible factor (HIF), a transcription factor, at the molecular level (1). Under normal oxygen conditions (normoxia), HIF-1␣ is hydroxylated, which promotes its binding to the ubiquitin ligase von Hippel-Lindau protein (pVHL), thereby targeting it for ubiquitin-proteasome system (UPS)-mediated degradation. However, under hypoxic conditions, HIF-1␣ becomes less hydroxylated, leading to its rapid accumulation and subsequent activation of hundreds of genes involved in cell survival, as well as genes involved in apoptosis (2). This opposing function of HIF in determining different cell fates is dependent on the physiopathological context and differential binding to other key partners, such as tumor suppressor protein p53.Similarly to HIF-1␣, p53 stability is also regulated by the hypoxic condition. p53 plays a crucial role in response to DNA damage, aberrant cell control, apoptosis, and senescence (3, 4). p53 function is constitutively regulated in different types of tumors under hypoxia by different mechanisms, such as p53 mutation, expression of inhibitors, or unknown host regulatory elements leading to induction of resistance to p53-mediated apoptosis. In normal cells, p53 protein expression is maintained at a low, often undetectable level due to ubiquitin-mediated proteasome degradation (5). Upon exposure to stress, such as oncogenic activation and certain hypoxic situations, p53 becomes stabilized. Consequently, p53 activates genes involved in cell cycle regulation and genes involved in apoptotic events (4).HIV-1 Tat-interacting protein 110 (Tip110), also known as "squamous cell carcinoma antigen recognized by T cells 3" (SA...

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Chaperoning of Mutant p53 Protein by Wild-type p53 Protein Causes Hypoxic Tumor Regression

Cited by 31 publications

References 34 publications

The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53

The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53

SCO2 Induces p53-Mediated Apoptosis by Thr⁸⁴⁵ Phosphorylation of ASK-1 and Dissociation of the ASK-1–Trx Complex

Tip110 Regulates the Cross Talk between p53 and Hypoxia-Inducible Factor 1α under Hypoxia and Promotes Survival of Cancer Cells

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Chaperoning of Mutant p53 Protein by Wild-type p53 Protein Causes Hypoxic Tumor Regression

Cited by 31 publications

References 34 publications

The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53

The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53

SCO2 Induces p53-Mediated Apoptosis by Thr845 Phosphorylation of ASK-1 and Dissociation of the ASK-1–Trx Complex

Tip110 Regulates the Cross Talk between p53 and Hypoxia-Inducible Factor 1α under Hypoxia and Promotes Survival of Cancer Cells

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SCO2 Induces p53-Mediated Apoptosis by Thr⁸⁴⁵ Phosphorylation of ASK-1 and Dissociation of the ASK-1–Trx Complex