ArticleMolecular and cellular biology2002
PIN1 is an E2F target gene essential for Neu/Ras-induced transformation of mammary epithelial cells.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.
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Who cites it
124 citing papers in PubMed, 1 synthesis or guideline pooled it, 250 citations in OpenAlex.
- The -842G/C polymorphisms of PIN1 contributes to cancer risk: a meta-analysis of 10 case-control studies.PloS one · 2013Pooled it
- Endogenous neuroprotection in vascular cognitive impairment and dementia.EBioMedicine · 2026Review
- Exploring the Research Progress of Vascular Dementia and Key Regulatory Molecules: E2F1.International journal of molecular sciences · 2026Review
- Telomere Maintenance and Oncogenesis.International journal of molecular sciences · 2025Review
- Bypassing the guardian: regulated cell death pathways in p53-mutant cancers.Cellular & molecular biology letters · 2025Review
- Non-canonical Function of Prolyl Hydroxylase Domain 2 in Breast Cancer Cell Growth and Progression: Role of Peptidyl-prolyl Cis-trans Isomerase NIMA-interacting 1.Journal of cancer prevention · 2024Article
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
- Stereospecific NANOG PEST Stabilization by Pin1.Biochemistry · 2024Article
- Review
- Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells.Nature communications · 2024Article
- PIN1P1 is activated by CREB1 and promotes gastric cancer progression via interacting with YBX1 and upregulating PIN1.Journal of cellular and molecular medicine · 2024Article
- The molecular mechanisms of peptidyl-prolylFrontiers in pharmacology · 2024Review
- The role of the Pin1-Frontiers in cell and developmental biology · 2024Review
- The role of the master cancer regulator Pin1 in the development and treatment of cancer.Frontiers in cell and developmental biology · 2024Review
- Interactions between the DNA Damage Response and the Telomere Complex in Carcinogenesis: A Hypothesis.Current issues in molecular biology · 2023Review
- Article
- Development of a contacting transwell co-culture system for theFrontiers in cell and developmental biology · 2023Article
- The kingdom of the prolyl-isomerase Pin1: The structural and functional convergence and divergence of Pin1.Frontiers in cell and developmental biology · 2022Review
- Cis P-tau underlies vascular contribution to cognitive impairment and dementia and can be effectively targeted by immunotherapy in mice.Science translational medicine · 2021Article
- Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy.Biomedicines · 2021Review
64 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Oncogenes Neu/HER2/ErbB2 and Ras can induce mammary tumorigenesis via upregulation of cyclin D1. One major regulatory mechanism in these oncogenic signaling pathways is phosphorylation of serines or threonines preceding proline (pSer/Thr-Pro). Interestingly, the pSer/Thr-Pro motifs in proteins exist in two completely distinct cis and trans conformations, whose conversion is catalyzed specifically by the essential prolyl isomerase Pin1. By isomerizing pSer/Thr-Pro bonds, Pin1 can regulate the conformation and function of certain phosphorylated proteins. We have previously shown that Pin1 is overexpressed in breast tumors and positively regulates cyclin D1 by transcriptional activation and posttranslational stabilization. Moreover, in Pin1 knockout mice, mammary epithelial cells fail to undergo massive proliferation during pregnancy, as is the case in cyclin D1 null mice. These results indicate that Pin1 is upregulated in breast cancer and may be involved in mammary tumors. However, the mechanism of Pin1 overexpression in cancer and its significance in cell transformation remain largely unknown. Here we demonstrate that PIN1 expression is mediated by the transcription factor E2F and enhanced by c-Neu and Ha-Ras via E2F. Furthermore, overexpression of Pin1 not only confers transforming properties on mammary epithelial cells but also enhances the transformed phenotypes of Neu/Ras-transformed mammary epithelial cells. In contrast, inhibition of Pin1 suppresses Neu- and Ras-induced transformed phenotypes, which can be fully rescued by overexpression of a constitutively active cyclin D1 mutant that is refractory to the Pin1 inhibition. Thus, Pin1 is an E2F target gene that is essential for the Neu/Ras-induced transformation of mammary epithelial cells through activation of cyclin D1.
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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.