Related Experiment Video

Updated: Oct 16, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

7.1K

YB-1 Oncoprotein Controls PI3K/Akt Pathway by Reducing Pten Protein Level

Antonella Delicato1, Eleonora Montuori1, Tiziana Angrisano1

  • 1Department of Biology, University of Naples Federico II, MSA-Via Cinthia, 26-80126 Naples, Italy.

Genes
|October 23, 2021
PubMed

Insights

The Y-box binding protein 1 (YB-1) oncoprotein reduces PTEN levels by controlling its mRNA, activating the PI3K/Akt pathway. This YB-1 activity promotes cancer cell survival and proliferation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Y-box binding protein 1 (YB-1) is an oncoprotein overexpressed in various cancers, regulating cell progression and proliferation.
  • YB-1's function is dependent on subcellular localization, primarily in the cytoplasm regulating mRNA translation and stability, but translocating to the nucleus as a prosurvival factor under stress.
  • YB-1 is implicated in regulating diverse signaling pathways and acts as a sensor for oxidative stress and DNA damage.

Purpose of the Study:

  • To investigate the role of YB-1 in regulating the PTEN/PI3K/Akt signaling pathway.
  • To determine the mechanism by which YB-1 influences PTEN levels.
  • To elucidate how YB-1 overexpression contributes to cancer cell survival and proliferation.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) to assess PTEN mRNA levels.
  • Cellular assays in human immortalized keratinocytes and HEK293T cells to evaluate YB-1 effects on PTEN.
  • Proteasome inhibition assays to investigate PTEN degradation.

Main Results:

  • YB-1 overexpression leads to reduced intracellular PTEN levels, consequently activating the PI3K/Akt pathway.
  • The reduction in PTEN levels mediated by YB-1 is observed in multiple cell types and is not reversed by proteasome inhibition.
  • YB-1 silencing results in increased PTEN mRNA levels, indicating negative transcriptional control.

Conclusions:

  • YB-1 negatively regulates PTEN at the transcript level.
  • YB-1 overexpression confers a survival and proliferative advantage to cancer cells, even those proficient in PTEN.
  • Targeting YB-1 may offer a therapeutic strategy for cancers driven by the PTEN/PI3K/Akt pathway.
Keywords:
PI3K/Akt pathwayPTENYB-1cold-shock proteinsproteasome

More Related Videos

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

578
Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.4K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.2K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.6K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.7K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
36.6K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.6K