ArticleCell death and differentiation2014
MDM2 restrains estrogen-mediated AKT activation by promoting TBK1-dependent HPIP degradation.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- In Silico Analysis Reveals MDM2 as a Potential Target of Ursolic Acid for Overcoming Tamoxifen Resistance in Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- 3'UTR RNA editing driven by ADAR1 modulates MDM2 expression in breast cancer cells.Functional & integrative genomics · 2025Article
- HPIP is an essential scaffolding protein running through the EGFR-RAS-ERK pathway and drives tumorigenesis.Science advances · 2023Article
- Identifying key multifunctional components shared by critical cancer and normal liver pathways via SparseGMM.Cell reports methods · 2023Article
- Review
- Article
- A novel chemical inhibitor suppresses breast cancer cell growth and metastasis through inhibiting HPIP oncoprotein.Cell death discovery · 2021Article
- PI3K/AKT signaling pathway as a critical regulator of Cisplatin response in tumor cells.Oncology research · 2021Review
- HPIP promotes epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer cells through PI3K/AKT pathway activation.Cellular oncology (Dordrecht, Netherlands) · 2017Article
- The role of MDM2 and MDM4 in breast cancer development and prevention.Journal of molecular cell biology · 2017Review
- HPIP: a predictor of lymph node metastasis and poor survival in cervical cancer.OncoTargets and therapy · 2017Article
- Expression of HPIP in epithelial ovarian carcinoma: a clinicopathological study.OncoTargets and therapy · 2017Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Restoration of p53 tumor suppressor function through inhibition of its interaction and/or enzymatic activity of its E3 ligase, MDM2, is a promising therapeutic approach to treat cancer. However, because the MDM2 targetome extends beyond p53, MDM2 inhibition may also cause unwanted activation of oncogenic pathways. Accordingly, we identified the microtubule-associated HPIP, a positive regulator of oncogenic AKT signaling, as a novel MDM2 substrate. MDM2-dependent HPIP degradation occurs in breast cancer cells on its phosphorylation by the estrogen-activated kinase TBK1. Importantly, decreasing Mdm2 gene dosage in mouse mammary epithelial cells potentiates estrogen-dependent AKT activation owing to HPIP stabilization. In addition, we identified HPIP as a novel p53 transcriptional target, and pharmacological inhibition of MDM2 causes p53-dependent increase in HPIP transcription and also prevents HPIP degradation by turning off TBK1 activity. Our data indicate that p53 reactivation through MDM2 inhibition may result in ectopic AKT oncogenic activity by maintaining HPIP protein levels.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.