Assembly, Target‐Signaling and Intracellular Transport of Tyrosinase Gene Family Proteins in the Initial Stage of Melanosome Biogenesis

Jimbow, Kowichi; Park, Jong Soo; Kato, Fumihiro; Hirosaki, Kuninori; Toyofuku, Kazutomo; Chen, Hua; Yamashita, Toshiharu

doi:10.1034/j.1600-0749.2000.130403.x

Cited by 111 publications

(84 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This scheme has been gradually revised as the complex nature of adapter protein complexes and the sorting mechanisms they direct has evolved. It is now known that TYR (and perhaps other melanosomal proteins) are sorted by means of the AP3 system to early endosomes, then to late endosomes, and eventually to melanosomes (16,(36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

A model for melanosome biogenesis based on the purification and analysis of early melanosomes

Kushimoto

Basrur

Valencia

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

215

263

View full text Add to dashboard Cite

Melanosome biogenesis and function were studied after purification of early stage melanosomes and characterization of specific proteins sorted to that organelle. Melanosomes were isolated from highly pigmented human MNT1 melanoma cells after disruption and initial separation by sucrose density gradient centrifugation. Low-density sucrose fractions were found by electron microscopy to be enriched in stage I and stage II melanosomes, and these fractions were further separated and purified by free flow electrophoresis. Tyrosinase and dopachrome tautomerase (DCT) activities were found exclusively in stage II melanosomes, even though DCT (and to some extent tyrosinase) proteins were sorted to stage I melanosomes. Western immunoblotting revealed that these catalytic proteins, as well as TYRP1, MART1, and GP100, were cleaved and inactivated in stage I melanosomes. Proteolytic cleavage was critical for the refolding of GP100 within the melanosomal milieu, and subsequent reorganization of amorphous stage I melanosomes into fibrillar, ovoid, and highly organized stage II melanosomes appears to stabilize the catalytic functions of melanosomal enzymes and allows melanin biosynthesis to begin. These results provide a better understanding of the structural features seen during melanosome biogenesis, and they yield further clues as to the physiological regulation of pigmentation.pigment ͉ melanin ͉ tyrosinase ͉ melanoma M ore than 95 distinct genes that play direct or indirect roles in mammalian pigmentation have been identified. Many of these genes encode proteins that are localized in melanosomes, specialized pigment organelles produced only by melanocytes. These gene products alter the quality or quantity of melanin produced and͞or the processing and distribution of melanosomes. The known melanosomal proteins are involved in melanogenesis as catalytic and͞or structural components. These include tyrosinase (TYR), the tyrosinase-related proteins-1 and -2 (TYRP1͞TRP1 and DCT͞TRP2, respectively; refs.

show abstract

Section: Discussionmentioning

confidence: 99%

A model for melanosome biogenesis based on the purification and analysis of early melanosomes

Kushimoto

Basrur

Valencia

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

215

263

View full text Add to dashboard Cite

show abstract

“…To study the presentation of an epitope derived from a retrotranslocated protein we chose the tyrosinase epitope Tyr369-377(D). Tyrosinase is a transmembrane glycoprotein produced in melanocytes and melanoma cells that is targeted to the ER (Jimbow et al, 2000;Petrescu et al, 2000). Misfolded tyrosinase is exported back to the cytosol where it is deglycosylated leading to the conversion of N371 to D371 through deamination (Skipper et al, 1996).…”

Section: Presentation Of Retrotranslocated Tyrosinase-derived Epitopementioning

confidence: 99%

Chaperone BAG6 is dispensable for MHC class I antigen processing and presentation

Bitzer

Basler

Groettrup

2016

Molecular Immunology

View full text Add to dashboard Cite

a b s t r a c tAntigen processing for direct presentation on MHC class I molecules is a multistep process requiring the concerted activity of several cellular complexes. The essential steps at the beginning of this pathway, namely protein synthesis at the ribosome and degradation via the proteasome, have been known for years. Nevertheless, there is a considerable lack of factors identified to function between protein synthesis and degradation during antigen processing. Here, we analyzed the impact of the chaperone BAG6 on MHC class I cell surface expression and presentation of virus-derived peptides. Although an essential role of BAG6 in antigen processing has been proposed previously, we found BAG6 to be dispensable in this pathway. Still, interaction of BAG6 and the model antigen tyrosinase was enhanced during proteasome inhibition pointing towards a role of BAG6 in antigen degradation. Redundant chaperone pathways potentially mask the contribution of BAG6 to antigen processing and presentation.

show abstract

“…In addition to protein stability, we tested the decay of HLA-A2 molecules complexed with Tyr 369 -377 , Mart-1 [27][28][29][30][31][32][33][34][35] , gp100 209 -217 , and gp100 280 -288 peptides. This was performed on brefeldin A-treated, peptide-pulsed T2 cells by flow cytometry with the TCR-like Abs.…”

Section: Determination Of Protein Stability and Its Correlation To Prmentioning

confidence: 99%

Expression Hierarchy of T Cell Epitopes from Melanoma Differentiation Antigens: Unexpected High Level Presentation of Tyrosinase-HLA-A2 Complexes Revealed by Peptide-Specific, MHC-Restricted, TCR-Like Antibodies

Michaeli

Denkberg²,

Sinik

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

Peptide Ags presented by class I MHC molecules on human melanomas and that are recognized by CD8؉ T cells are the subjects of many studies of antitumor immunity and represent attractive candidates for therapeutic approaches. However, no direct quantitative measurements exist to reveal their expression hierarchy on the cell surface. Using novel recombinant Abs which bind these Ags with a peptide-specific, MHC-restricted manner, we demonstrate a defined pattern of expression hierarchy of peptide-HLA-A2 complexes derived from three major differentiation Ags: gp100, Melan-A/Mart-1, and tyrosinase. Studying melanoma cell lines derived from multiple patients, we reveal a surprisingly high level of presentation of tyrosinase-derived complexes and moderate to very low expression of complexes derived from other Ags. No correlation between Ag presentation and mRNA expression was found; however, protein stability may play a major role. These results provide new insights into the characteristics of Ag presentation and are particularly important when such targets are being considered for immunotherapy. These results may shed new light on relationships between Ag presentation and immune response to cancer Ags.

show abstract

Assembly, Target‐Signaling and Intracellular Transport of Tyrosinase Gene Family Proteins in the Initial Stage of Melanosome Biogenesis

Cited by 111 publications

References 31 publications

A model for melanosome biogenesis based on the purification and analysis of early melanosomes

A model for melanosome biogenesis based on the purification and analysis of early melanosomes

Chaperone BAG6 is dispensable for MHC class I antigen processing and presentation

Expression Hierarchy of T Cell Epitopes from Melanoma Differentiation Antigens: Unexpected High Level Presentation of Tyrosinase-HLA-A2 Complexes Revealed by Peptide-Specific, MHC-Restricted, TCR-Like Antibodies

Contact Info

Product

Resources

About