Related Experiment Video

Updated: Nov 11, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

9.1K

USP22 promotes melanoma and BRAF inhibitor resistance via YAP stabilization

Ying Wei1, Ziyun Jiang2, Jianfeng Lu1

  • 1Department of Plastic and Reconstructive Surgery, Changxing People's Hospital, Huzhou, Zhejiang 313100, P.R. China.

Oncology Letters
|March 29, 2021
PubMed

Insights

Ubiquitin-specific peptidase 22 (USP22) controls Yes-associated protein (YAP) levels in melanoma, impacting tumor growth and drug resistance. Targeting the USP22/YAP pathway may offer new melanoma treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Yes-associated protein (YAP) is a key regulator of organ size and tumorigenesis, and its overexpression is linked to BRAF inhibitor resistance in melanoma.
  • The precise mechanisms driving YAP overexpression in melanoma remain largely unelucidated.
  • Understanding YAP regulation is crucial for developing effective melanoma therapies.

Purpose of the Study:

  • To identify and characterize the role of deubiquitinases in regulating YAP abundance and function in melanoma.
  • To investigate the relationship between ubiquitin-specific peptidase 22 (USP22) and YAP in melanoma.
  • To explore the therapeutic potential of targeting the USP22/YAP axis in melanoma, particularly in the context of BRAF inhibitor resistance.

Main Methods:

  • Western blotting and immunohistochemical staining were employed to assess USP22 and YAP expression in melanoma cell lines and patient samples.
  • Co-immunoprecipitation assays were used to confirm the interaction between USP22 and YAP.
  • Functional assays were performed to evaluate the impact of USP22 depletion or overexpression on YAP levels, cell proliferation, tumorigenesis, and vemurafenib resistance.

Main Results:

  • USP22 expression was found to be positively associated with YAP expression in melanoma.
  • USP22 directly interacted with and deubiquitinated YAP, thereby preventing its degradation.
  • Depletion of USP22 led to decreased YAP expression, suppressed melanoma cell proliferation and tumorigenesis, and reduced vemurafenib resistance.

Conclusions:

  • USP22 functions as a deubiquitinase that stabilizes YAP protein levels in melanoma.
  • The USP22/YAP axis plays a significant role in melanoma progression and resistance to BRAF inhibitors like vemurafenib.
  • Targeting the USP22/YAP pathway presents a promising therapeutic strategy for overcoming BRAF inhibitor resistance in melanoma.
Keywords:
BRAF inhibitormelanomaresistancetumorigenesisubiquitin-specific peptidase 22yes-associated protein

More Related Videos

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

7.2K
Y-27632 Enriches the Yield of Human Melanocytes from Adult Skin Tissues08:06

Y-27632 Enriches the Yield of Human Melanocytes from Adult Skin Tissues

Published on: July 8, 2020

5.8K

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...
4.8K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.0K
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...
7.3K
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...
4.0K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.8K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.4K