ArticleMolecular biology of the cell2002
Pink-eyed dilution protein modulates arsenic sensitivity and intracellular glutathione metabolism.
Article in Molecular biology of the cell, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Association between a germline OCA2 polymorphism at chromosome 15q13.1 and estrogen receptor-negative breast cancer survival.Journal of the National Cancer Institute · 2010Pooled it
- Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians.International journal of cancer · 2009Trial
- Genetic Analysis of 28 Chinese Families With Tyrosinase-Positive Oculocutaneous Albinism.Frontiers in genetics · 2021Article
- The Evolution of Silicon Transport in Eukaryotes.Molecular biology and evolution · 2016Article
- A Genetic Mechanism for Convergent Skin Lightening during Recent Human Evolution.Molecular biology and evolution · 2016Article
- Unrevealing the role of P-protein on melanosome biology and structure, using siRNA-mediated down regulation of OCA2.Molecular and cellular biochemistry · 2015Article
- Loss of Oca2 disrupts the unfolded protein response and increases resistance to endoplasmic reticulum stress in melanocytes.Pigment cell & melanoma research · 2013Article
- Evaluation of the role of glutathione in the lead-induced toxicity in Saccharomyces cerevisiae.Current microbiology · 2013Article
- DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics.Human mutation · 2013Review
- Report of a novel OCA2 gene mutation and an investigation of OCA2 variants on melanoma risk in a familial melanoma pedigree.Journal of dermatological science · 2013Article
- A global view of the OCA2-HERC2 region and pigmentation.Human genetics · 2012Article
- Ascorbate and thiol antioxidants abolish sensitivity of yeast Saccharomyces cerevisiae to disulfiram.Cell biology and toxicology · 2012Article
- Informed reasoning: repositioning of nitisinone to treat oculocutaneous albinism.The Journal of clinical investigation · 2011Article
- Functional interactions between OCA2 and the protein complexes BLOC-1, BLOC-2, and AP-3 inferred from epistatic analyses of mouse coat pigmentation.Pigment cell & melanoma research · 2011Article
- The yeast CLC protein counteracts vesicular acidification during iron starvation.Journal of cell science · 2010Article
- Involvement of ABC transporters in melanogenesis and the development of multidrug resistance of melanoma.Pigment cell & melanoma research · 2009Review
- Influence of melanosome dynamics on melanoma drug sensitivity.Journal of the National Cancer Institute · 2009Article
- Localization to mature melanosomes by virtue of cytoplasmic dileucine motifs is required for human OCA2 function.Molecular biology of the cell · 2009Article
- Melanosomes--dark organelles enlighten endosomal membrane transport.Nature reviews. Molecular cell biology · 2007Review
- A role for tyrosinase-related protein 1 in 4-tert-butylphenol-induced toxicity in melanocytes: Implications for vitiligo.The American journal of pathology · 2006Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the mouse p (pink-eyed dilution) and human P genes lead to melanosomal defects and ocular developmental abnormalities. Despite the critical role played by the p gene product in controlling tyrosinase processing and melanosome biogenesis, its precise biological function is still not defined. We have expressed p heterologously in the yeast Saccharomyces cerevisiae to study its function in greater detail. Immunofluorescence studies revealed that p reaches the yeast vacuolar membrane via the prevacuolar compartment. Yeast cells expressing p exhibited increased sensitivity to a number of toxic compounds, including arsenicals. Similarly, cultured murine melanocytes expressing a functional p gene were also found to be more sensitive to arsenical compounds compared with p-null cell lines. Intracellular glutathione, known to play a role in detoxification of arsenicals, was diminished by 50% in p-expressing yeast. By using the glutathione-conjugating dye monochlorobimane, in combination with acivicin, an inhibitor of vacuolar gamma-glutamyl cysteine transpeptidase, involved in the breakdown of glutathione, we found that p facilitates the vacuolar accumulation of glutathione. Our data demonstrate that the pink-eyed dilution protein increases cellular sensitivity to arsenicals and other metalloids and can modulate intracellular glutathione metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.