Related Experiment Video

Updated: May 30, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Regulation of MITF stability by the USP13 deubiquitinase

Xiansi Zhao1, Brian Fiske, Akinori Kawakami

  • 1Cutaneous Biology Research Center & Melanoma Program, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.

Nature Communications
|August 4, 2011
PubMed

Insights

Ubiquitin-specific protease 13 (USP13) deubiquitinates and stabilizes microphthalmia-associated transcription factor (MITF). USP13 is essential for melanoma cell growth, suggesting it as a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • Microphthalmia-associated transcription factor (MITF) is crucial for melanocyte development and is often dysregulated in melanoma.
  • MAPK pathway activation in melanoma leads to MITF degradation, but the enzymes controlling MITF ubiquitination/deubiquitination remain largely unknown.

Purpose of the Study:

  • To identify enzymes responsible for microphthalmia-associated transcription factor (MITF) deubiquitination.
  • To investigate the role of USP13 in regulating MITF levels and melanoma progression.

Main Methods:

  • Utilized a short hairpin RNA library targeting deubiquitinating enzymes to screen for MITF-interacting proteases.
  • Performed knockdown experiments to assess the impact of USP13 on MITF protein and mRNA levels.
  • Analyzed the effect of USP13 on MITF downstream gene expression and melanoma cell proliferation in vitro and in vivo.

Main Results:

  • Identified ubiquitin-specific protease 13 (USP13) as a key deubiquitinating enzyme for MITF.
  • USP13 stabilizes MITF protein levels, while USP13 suppression leads to MITF degradation without affecting its mRNA.
  • USP13 modulates MITF target gene expression, promoting melanoma growth in soft agar and in mouse models.

Conclusions:

  • USP13 plays a critical role in stabilizing MITF protein levels through deubiquitination.
  • USP13 is essential for melanoma cell growth and progression.
  • USP13 represents a potential therapeutic target for melanoma treatment.

More Related Videos

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model09:00

Comparative Strategies for Ubiquitination Detection in Mammalian Cell Lysates Using SMAD2/SMURF2 as a Model

Published on: April 17, 2026

Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples09:45

Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples

Published on: May 10, 2015

Related Concept Videos

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.
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
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 daughter...
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...
mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability