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Oncogenic function of p34SEI-1 via NEDD4‑1‑mediated PTEN ubiquitination/degradation and activation of the PI3K/AKT
Samil Jung1, Chengping Li, Dongjun Jeong
1Department of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Abstract:
A 34-KD protein encoded by the SEI-1 gene (p34(SEI‑1)), is a relatively recently discovered oncoprotein that has multiple important biological functions. Our data show that p34(SEI-1) enhances cancer cell survival and promotes tumorigenesis by downregulating the tumor suppressor PTEN, a negative regulator of the PI3K/AKT signaling pathway, and therefore activating the PI3K/AKT signaling pathway. In this process, p34(SEI-1) positively affects NEDD4-1 gene expression both at the transcriptional and protein levels. Furthermore, the expression levels of p34(SEI-1) and NEDD4-1 were found to be coordinated in tumor tissues obtained from patients with breast cancer. We also show that p34(SEI-1) affects the subcellular localization of PTEN.
Insights
The oncoprotein p34(SEI-1) promotes cancer by downregulating the tumor suppressor PTEN, activating the PI3K/AKT pathway, and increasing NEDD4-1 expression. Its levels correlate with breast cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- p34(SEI-1) is a recently identified oncoprotein with significant biological roles.
- The Phosphatidylinositol 3-kinase/AKT (PI3K/AKT) signaling pathway is crucial in cell survival and cancer development.
- PTEN acts as a tumor suppressor by negatively regulating the PI3K/AKT pathway.
Purpose of the Study:
- To investigate the role of p34(SEI-1) in cancer cell survival and tumorigenesis.
- To elucidate the molecular mechanisms by which p34(SEI-1) influences the PTEN/PI3K/AKT pathway.
- To examine the relationship between p34(SEI-1) and NEDD4-1 expression in breast cancer.
Main Methods:
- Analysis of gene and protein expression levels.
- Investigation of signaling pathway activation.
- Assessment of protein subcellular localization.
- Correlation studies in patient tumor tissues.
Main Results:
- p34(SEI-1) enhances cancer cell survival and promotes tumorigenesis.
- p34(SEI-1) downregulates PTEN, leading to PI3K/AKT pathway activation.
- p34(SEI-1) positively regulates NEDD4-1 expression transcriptionally and post-translationally.
- Expression of p34(SEI-1) and NEDD4-1 is coordinated in breast cancer tissues.
- p34(SEI-1) influences PTEN's subcellular localization.
Conclusions:
- p34(SEI-1) is an oncoprotein that drives cancer progression via PTEN downregulation and PI3K/AKT pathway activation.
- NEDD4-1 is a downstream target of p34(SEI-1), and their coordinated expression is relevant in breast cancer.
- Targeting p34(SEI-1) or its downstream effectors may offer therapeutic strategies for cancer.
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