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Updated: May 11, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Pin1 regulates the dynamics of c-Myc DNA binding to facilitate target gene regulation and oncogenesis
Amy S Farrell1, Carl Pelz, Xiaoyan Wang
1Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, USA.
Abstract:
The Myc oncoprotein is considered a master regulator of gene transcription by virtue of its ability to modulate the expression of a large percentage of all genes. However, mechanisms that direct Myc's recruitment to DNA and target gene selection to elicit specific cellular functions have not been well elucidated. Here, we report that the Pin1 prolyl isomerase enhances recruitment of serine 62-phosphorylated Myc and its coactivators to select promoters during gene activation, followed by promoting Myc's release associated with its degradation. This facilitates Myc's activation of genes involved in cell growth and metabolism, resulting in enhanced proproliferative activity, even while controlling Myc levels. In cancer cells with impaired Myc degradation, Pin1 still enhances Myc DNA binding, although it no longer facilitates Myc degradation. Thus, we find that Pin1 and Myc are cooverexpressed in cancer, and this drives a gene expression pattern that we show is enriched in poor-outcome breast cancer subtypes. This study provides new insight into mechanisms regulating Myc DNA binding and oncogenic activity, it reveals a novel role for Pin1 in the regulation of transcription factors, and it elucidates a mechanism that can contribute to oncogenic cooperation between Pin1 and Myc.
Insights
Pin1 enhances the DNA binding of Myc, a key cancer oncoprotein, promoting cell growth and proliferation. This interaction is crucial in cancer, particularly in aggressive breast cancer subtypes.
Area of Science:
- Molecular Biology
- Cancer Biology
- Biochemistry
Background:
- The Myc oncoprotein is a master regulator of gene transcription, influencing a vast number of genes.
- Mechanisms governing Myc's DNA recruitment and target gene specificity remain incompletely understood.
Purpose of the Study:
- To elucidate the role of Pin1 prolyl isomerase in regulating Myc's transcriptional activity and oncogenic function.
- To investigate the interplay between Pin1 and Myc in gene regulation and cancer progression.
Main Methods:
- Investigated the effect of Pin1 on serine 62-phosphorylated Myc recruitment to DNA.
- Analyzed Myc's gene activation, degradation, and association with coactivators.
- Examined Pin1 and Myc co-expression in cancer cell lines and patient data, including breast cancer subtypes.
Main Results:
- Pin1 enhances the recruitment of phosphorylated Myc and coactivators to specific gene promoters, facilitating gene activation.
- Pin1 promotes Myc release from DNA, which is linked to Myc degradation and regulation of cell growth and metabolism.
- In cancer cells with defective Myc degradation, Pin1 still boosts Myc DNA binding but not degradation, leading to cooverexpression and a poor-outcome gene expression pattern in breast cancer.
Conclusions:
- Pin1 plays a novel role in regulating transcription factors, specifically enhancing Myc's DNA binding and oncogenic activity.
- The Pin1-Myc interaction contributes to oncogenic cooperation and drives a gene expression profile associated with poor prognosis in certain breast cancers.
- Understanding this mechanism offers new insights into Myc regulation and potential therapeutic strategies targeting Pin1 and Myc in cancer.
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