Related Experiment Video

Updated: Oct 18, 2025

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

2.8K

26S Proteasome Non-ATPase Regulatory Subunits 1 (PSMD1) and 3 (PSMD3) as Putative Targets for Cancer Prognosis and

Andres J Rubio1, Alfonso E Bencomo-Alvarez2, James E Young3

  • 1Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center at El Paso, El Paso, TX 79905, USA.

Cells
|September 28, 2021
PubMed

Insights

Targeting PSMD1 and PSMD3, components of the 26S proteasome, shows promise for cancer therapy. These proteins are upregulated in various cancers, suggesting their potential as novel therapeutic targets for improved patient outcomes.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Proteomics

Background:

  • The ubiquitin proteasome system is a validated target for cancer therapy, with drugs like bortezomib approved for certain hematological malignancies.
  • Existing proteasome inhibitors face challenges including adverse effects and drug resistance, necessitating the exploration of alternative therapeutic strategies.
  • Previous research indicated that inhibiting 19S regulatory components, PSMD1 and PSMD3, selectively induced apoptosis in chronic myeloid leukemia (CML) cells.

Purpose of the Study:

  • To investigate the potential of PSMD1 and PSMD3 as novel anti-cancer therapeutic targets.
  • To determine the expression levels of PSMD1 and PSMD3 in various cancer types compared to normal tissues.
  • To assess the correlation between PSMD1 and PSMD3 expression and patient overall survival.

Main Methods:

  • Utilized The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases for analysis.
  • Examined mRNA and protein expression levels of PSMD1 and PSMD3 in cancerous versus normal tissues.
  • Correlated PSMD1 and PSMD3 expression data with overall survival statistics.

Main Results:

  • PSMD1 and PSMD3 exhibit altered expression in cancerous tissues compared to normal controls across multiple cancer types.
  • Expression levels of PSMD1 and PSMD3 show a correlation with patient overall survival, indicating prognostic value.
  • These findings support the hypothesis that PSMD1 and PSMD3 are relevant beyond CML and may serve as broader cancer targets.

Conclusions:

  • PSMD1 and PSMD3 represent promising novel targets for cancer therapy and prognosis.
  • Further investigation into PSMD1 and PSMD3 as therapeutic targets is warranted.
  • Targeting these proteasome subunits could offer a new avenue for overcoming limitations of current cancer treatments.
Keywords:
cancerdrug targetsoncogenesproteasome inhibition

More Related Videos

Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors08:08

Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors

Published on: February 27, 2015

16.5K
Phosphopeptide Enrichment Coupled with Label-free Quantitative Mass Spectrometry to Investigate the Phosphoproteome in Prostate Cancer12:23

Phosphopeptide Enrichment Coupled with Label-free Quantitative Mass Spectrometry to Investigate the Phosphoproteome in Prostate Cancer

Published on: August 2, 2018

12.3K

Related Concept Videos

The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
9.3K
The Proteasome Structure01:17

The Proteasome Structure

The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
1.1K
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
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.0K