Related Experiment Video

Updated: Jun 23, 2026

miRNA Expression Analyses in Prostate Cancer Clinical Tissues
11:29

miRNA Expression Analyses in Prostate Cancer Clinical Tissues

Published on: September 8, 2015

Expression, regulation and function of the ISGylation system in prostate cancer

A Kiessling1, C Hogrefe, S Erb

  • 1Medical Faculty, Institute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, Germany. Andrea.Kiessling@novartis.com

Oncogene
|May 12, 2009
PubMed

Insights

Interferon-stimulated gene 15 (ISG15) and its conjugation enzymes are upregulated in prostate cancer (PCa) tumors. This ISGylation system modulates androgen receptor (AR) expression and PCa cell proliferation, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The androgen receptor (AR) is critical for prostate cell proliferation and prostate cancer (PCa) progression.
  • Understanding AR regulation offers potential new PCa treatment strategies.

Purpose of the Study:

  • To investigate the role of interferon-stimulated gene 15 (ISG15) conjugation in AR regulation and PCa cell proliferation.
  • To determine if ISGylation components are differentially expressed in PCa tissues and correlate with treatment status.

Main Methods:

  • Analysis of ISG15 and conjugation enzyme expression in PCa tumor samples versus non-malignant tissues.
  • In vitro studies using PCa cell lines to assess androgen-mediated regulation of ISGylation components.
  • Investigating the effect of Ube1L (a key ISGylation factor) overexpression and knockdown on AR expression and cell proliferation.

Main Results:

  • ISG15 and its conjugation enzymes were upregulated in PCa tumors compared to normal tissues.
  • Expression levels differed significantly between patients treated with and without androgen ablation.
  • ISGylation system components were confirmed to be androgen-mediated and AR-dependent.
  • Overexpression of Ube1L increased AR mRNA and protein levels, enhancing proliferation even without androgens.
  • Ube1L knockdown led to decreased AR expression.

Conclusions:

  • The ISGylation system modulates AR expression and influences PCa cell proliferation.
  • This study reveals a novel function of the ISGylation system in prostate cancer development and progression.
  • Targeting the ISGylation pathway presents a potential new therapeutic approach for PCa.

Related Concept Videos

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 activation may...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...