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Updated: Oct 31, 2025

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Published on: July 25, 2019
Deubiquitination of MITF-M Regulates Melanocytes Proliferation and Apoptosis
Shuaishuai Hu1, Shaocheng Bai1, Yingying Dai1
1College of Animal Science and Technology, Yangzhou University, Yangzhou, China.
Abstract:
Microphthalmia-associated transcription factor-M (MITF-M) is the key gene in the proliferation and differentiation of melanocytes, which undergoes an array of post-translation modifications. As shown in our previous study, deubiquitinase USP13 is directly involved in melanogenesis. However, it is still ambiguous that the effect of USP13-mediated MITF-M expression on melanocytes proliferation and apoptosis. Herein, we found that MITF-M overexpressing melanocytes showed high cell proliferation, reduced apoptosis, and increased melanin levels. Besides, melanin-related genes, TYR, DCT, GPNMB, and PMEL, were significantly up-regulated in MITF-M overexpressing melanocytes. Furthermore, Exogenous USP13 significantly upregulated the endogenous MITF-M protein level, downregulated USP13 significantly inhibited MITF-M protein levels, without altering MITF-M mRNA expression. In addition, USP13 upregulation mitigated the MITF-M degradation and significantly increased the half-life of MITF-M. Also, USP13 stabilized the exogenous MITF protein levels. In conclusion, the MITF-M level was regulated by USP13 deubiquitinase in melanocytes, affecting melanocytes proliferation and apoptosis. This study provides the theoretical basis for coat color transformation that could be useful in the development of the new breed in fur animals.
Insights
The deubiquitinase USP13 regulates Microphthalmia-associated transcription factor-M (MITF-M) protein levels in melanocytes, impacting cell proliferation and apoptosis. This finding offers insights into coat color development in fur animals.
Area of Science:
- Cell Biology
- Genetics
- Dermatology
Background:
- Microphthalmia-associated transcription factor-M (MITF-M) is crucial for melanocyte proliferation and differentiation.
- Deubiquitinase USP13 has been previously linked to melanogenesis.
- The precise role of USP13 in regulating MITF-M and its downstream effects on melanocytes remained unclear.
Purpose of the Study:
- To investigate the effect of USP13 on MITF-M expression and its subsequent impact on melanocyte proliferation and apoptosis.
- To elucidate the mechanism by which USP13 influences MITF-M protein stability.
Main Methods:
- Overexpression of MITF-M in melanocytes.
- Manipulation of USP13 levels (exogenous and downregulation) in melanocytes.
- Analysis of cell proliferation, apoptosis, melanin levels, and expression of melanin-related genes (TYR, DCT, GPNMB, PMEL).
- Assessment of MITF-M protein and mRNA levels, and protein half-life.
Main Results:
- MITF-M overexpression led to increased melanocyte proliferation, reduced apoptosis, and elevated melanin levels.
- Melanin-related genes were significantly upregulated in MITF-M overexpressing cells.
- USP13 modulated endogenous MITF-M protein levels without affecting MITF-M mRNA, indicating post-transcriptional regulation.
- USP13 stabilized MITF-M protein, increasing its half-life and mitigating degradation.
Conclusions:
- USP13 deubiquitinase regulates MITF-M protein levels in melanocytes, influencing their proliferation and apoptosis.
- This regulatory mechanism provides a theoretical basis for coat color transformation and potential applications in fur animal breeding.
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