Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Abnormal Proliferation

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...

Negative Regulator Molecules

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.

The Retinoblastoma Gene

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,...

The Intrinsic Apoptotic Pathway

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...

MAPK Signaling Cascades

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...

Receptor Downregulation in MVBs

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...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

The Imipridone ONC206 Inhibits Tumor Growth and Improves Survival in Patient-Derived Xenograft Models of Uveal Melanoma.

Cancers·2026

Same author

Personalized targeting of BCL2 family proteins overcomes acquired resistance to BRAF-MEK inhibitors in preclinical melanoma.

Nature communications·2026

Same author

Meeting Report From the 2025 Cure Ocular Melanoma (CURE OM) Global Science Meeting, Amsterdam, the Netherlands, October 2025.

Pigment cell & melanoma research·2026

Same author

Editor's Note: Inhibition of NF-κB-Dependent Signaling Enhances Sensitivity and Overcomes Resistance to BET Inhibition in Uveal Melanoma.

Cancer research·2026

Same author

Melanoma-patient-derived xenograft multi-omics resource melPDomiX maps gain- and loss-of-function alterations.

Cell reports·2026

Same author

Germline variants in cancer susceptibility genes among patients with mucosal melanoma.

NPJ genomic medicine·2026

Search research articles

Related Experiment Video

Updated: Apr 7, 2026

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

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

Published on: June 7, 2019

RAC1 P29S regulates PD-L1 expression in melanoma.

Ha Linh Vu¹, Sheera Rosenbaum¹, Timothy J Purwin¹

¹Department of Cancer Biology and Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.

Pigment Cell & Melanoma Research

|July 16, 2015

Summary

This summary is machine-generated.

RAC1 P29 mutations in melanoma increase PD-L1 expression, potentially suppressing antitumor immunity. This finding offers new insights into melanoma biology and suggests PD-L1 as a biomarker for immunotherapy response.

Keywords:

PD-L1 RAC1 anti-PD-1 immune evasion melanoma

More Related Videos

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

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

Published on: March 27, 2020

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

Related Experiment Videos

Last Updated: Apr 7, 2026

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

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

Published on: June 7, 2019

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

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

Published on: March 27, 2020

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

Area of Science:

Oncology
Molecular Biology
Immunology

Background:

Whole exome sequencing identifies RAC1 P29 mutations in 5-9% of cutaneous melanoma cases.
The precise biological role of RAC1 P29 mutations in melanoma remains largely undetermined.

Purpose of the Study:

To elucidate the functional consequences of RAC1 P29 mutations in melanoma.
To investigate the impact of RAC1 P29 mutations on protein expression and immune response.

Main Methods:

Reverse phase protein array (RPPA) analysis to assess protein and phospho-protein expression changes.
Analysis of The Cancer Genome Atlas (TCGA) melanoma patient samples.

Main Results:

RAC1 P29S expression upregulated cyclin B1, PD-L1, Ets-1, and Syk.
PD-L1 expression was significantly increased in patients with RAC1 P29S mutations compared to wild-type (WT) and other RAC1 mutants.
Upregulation of PD-L1 suggests RAC1 P29S may promote immune suppression.

Conclusions:

Oncogenic RAC1 P29S mutations promote PD-L1 upregulation in melanoma.
This PD-L1 increase may contribute to the suppression of the antitumor immune response.
RAC1 P29S-driven PD-L1 expression presents a potential biomarker for anti-PD1/anti-PD-L1 immunotherapy efficacy.