Related Experiment Video

Updated: Jul 30, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

13.2K

Protein Levels of Anti-Apoptotic Mcl-1 and the Deubiquitinase USP9x Are Cooperatively Upregulated during Prostate

Sophia A Hogh-Binder1, Diana Klein2, Frederik Wolfsperger1

  • 1Department of Radiation Oncology, University Hospital Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany.

Cancers
|May 13, 2023
PubMed
Abstract

Insights

High levels of Mcl-1 and USP9x are linked to advanced prostate cancer and radiotherapy resistance. Targeting USP9x reduces Mcl-1, increasing cancer cell sensitivity to radiation therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Radiotherapy is a key treatment for prostate cancer, but resistance limits its effectiveness.
  • The Bcl-2 protein family regulates apoptosis and influences radiotherapy sensitivity.
  • Mcl-1 (an anti-apoptotic protein) and USP9x (a deubiquitinase stabilizing Mcl-1) are implicated in cancer progression.

Purpose of the Study:

  • To investigate the roles of Mcl-1 and USP9x in prostate cancer progression and response to radiotherapy.
  • To understand how Mcl-1 and USP9x influence prostate cancer cell sensitivity to radiation.

Main Methods:

  • Immunohistochemistry to assess Mcl-1 and USP9x levels during cancer progression.
  • siRNA-mediated knockdown to neutralize Mcl-1 and USP9x.
  • Cycloheximide treatment to analyze Mcl-1 stability.
  • Flow cytometry and colony formation assays to evaluate cell death and clonogenic potential.

Main Results:

  • Mcl-1 and USP9x protein levels increase with prostate cancer progression, correlating with advanced stages.
  • Mcl-1 stability influences its protein levels in prostate cancer cells (LNCaP and PC3).
  • Radiotherapy affects Mcl-1 protein turnover; USP9x knockdown in LNCaP cells decreases Mcl-1 and enhances radiotherapy sensitivity.

Conclusions:

  • Posttranslational regulation of protein stability contributes to elevated Mcl-1 levels.
  • USP9x deubiquitinase regulates Mcl-1 levels in prostate cancer cells.
  • USP9x inhibition represents a potential strategy to overcome radiotherapy resistance in prostate cancer.
Keywords:
Mcl-1USP9xprostate cancerprotein stabilityradiotherapyubiquitylation

More Related Videos

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

13.4K
miRNA Expression Analyses in Prostate Cancer Clinical Tissues11:29

miRNA Expression Analyses in Prostate Cancer Clinical Tissues

Published on: September 8, 2015

10.9K

Related Concept Videos

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...
4.6K
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...
3.8K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
6.9K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.7K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.1K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K