This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jäger, D. Articles by Chen, Y.-T. Search for Related Content PubMed PubMed Citation Articles by Jäger, D. Articles by Chen, Y.-T.

Serological Cloning of a Melanocyte rab Guanosine 5'-Triphosphate-binding Protein and a Chromosome Condensation Protein from a Melanoma Complementary DNA Library¹

Department of Pathology, Weill Medical College of Cornell University (D. J., Y.-T. C.), and Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center (E. S., A. O. G., M. J. S., L. J. O.), New York, New York 10021; and Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, 60488 Frankfurt, Germany (D. J., E. J., A. K.)

Characterization of immunogenic human melanoma antigens has been a major focus of tumor immunologists over the past two decades, and a broad array of antigens recognized by antibodies and T cells in the autologous host has been defined. In the present study, a melanoma library was screened by SEREX (serological analysis of cDNA expression libraries), and 43 genes were isolated, 2 of which, NY-MEL-1 and NY-MEL-3, encode novel gene products with differential tissue expression. NY-MEL-1 encodes a new rab GTP-binding protein, rab38. Among >40 rab proteins, rab38 has a unique COOH terminus which would allow posttranslational farnesylation and palmitoylation, lipid modifications normally occurring in ras proteins but not in other rab proteins. It is also the only rab gene showing a predominant mRNA expression in melanocytes, a cell-specific expression pattern likely related to melanosomal transport and docking. Northern blot analysis showed no detectable expression in other normal tissues. Consistent with this lineage specificity, rab38 mRNA is expressed in 80–90% of melanoma (17 of 19), but rarely in nonmelanocytic malignancies (1 of 16). The second novel gene isolated, NY-MEL-3, encodes a mitotic protein highly homologous to the Xenopus chromosome condensation protein XCAP-G, designated hCAP-G. Analysis of hCAP-G mRNA expression showed highest expression in the testis among normal tissues and variable expression in tumor cells, reflecting the proliferative activity in these cells. This mitosis-related expression suggests hCAP-G as a possible proliferation marker and a potential prognostic indicator in cancer. These findings provide further support that SEREX can define biologically significant molecules in cancer.

This article has been cited by other articles:

				K. Osanai, R. Oikawa, J. Higuchi, M. Kobayashi, K. Tsuchihara, M. Iguchi, H. Jongsu, H. Toga, and D. R. Voelker A Mutation in Rab38 Small GTPase Causes Abnormal Lung Surfactant Homeostasis and Aberrant Alveolar Structure in Mice Am. J. Pathol., November 1, 2008; 173(5): 1265 - 1274. [Abstract] [Full Text] [PDF]

				B. P. Brooks, D. M. Larson, C.-C. Chan, S. Kjellstrom, R. S. Smith, M. A. Crawford, L. Lamoreux, M. Huizing, R. Hess, X. Jiao, et al. Analysis of Ocular Hypopigmentation in Rab38cht/cht Mice Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 3905 - 3913. [Abstract] [Full Text] [PDF]

				S. M. Walton, M. Gerlinger, O. de la Rosa, N. Nuber, A. Knights, A. Gati, M. Laumer, L. Strauss, C. Exner, N. Schafer, et al. Spontaneous CD8 T Cell Responses against the Melanocyte Differentiation Antigen RAB38/NY-MEL-1 in Melanoma Patients J. Immunol., December 1, 2006; 177(11): 8212 - 8218. [Abstract] [Full Text] [PDF]

				C. Wasmeier, M. Romao, L. Plowright, D. C. Bennett, G. Raposo, and M. C. Seabra Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes J. Cell Biol., October 23, 2006; 175(2): 271 - 281. [Abstract] [Full Text] [PDF]

				M. S. Marks Darkness descends with two Rabs J. Cell Biol., October 23, 2006; 175(2): 199 - 200. [Abstract] [Full Text] [PDF]

				T. Okada, M. Akada, T. Fujita, T. Iwata, Y. Goto, K. Kido, T. Okada, Y. Matsuzaki, K. Kobayashi, S. Matsuno, et al. A Novel Cancer Testis Antigen That Is Frequently Expressed in Pancreatic, Lung, and Endometrial Cancers Clin. Cancer Res., January 1, 2006; 12(1): 191 - 197. [Abstract] [Full Text] [PDF]

				P. S. Steeg New Insights into the Tumor Metastatic Process Revealed by Gene Expression Profiling Am. J. Pathol., May 1, 2005; 166(5): 1291 - 1294. [Full Text] [PDF]

				S. Yamada, M. Komatsu, Y. Sato, K. Yamauchi, T. Aizawa, and I. Kojima Nutrient Modulation of Palmitoylated 24-Kilodalton Protein in Rat Pancreatic Islets Endocrinology, December 1, 2003; 144(12): 5232 - 5241. [Abstract] [Full Text] [PDF]

				M. J. Scanlan, S. Welt, C. M. Gordon, Y.-T. Chen, A. O. Gure, E. Stockert, A. A. Jungbluth, G. Ritter, D. Jager, E. Jager, et al. Cancer-related Serological Recognition of Human Colon Cancer: Identification of Potential Diagnostic and Immunotherapeutic Targets Cancer Res., July 15, 2002; 62(14): 4041 - 4047. [Abstract] [Full Text] [PDF]

				S. K. Loftus, D. M. Larson, L. L. Baxter, A. Antonellis, Y. Chen, X. Wu, Y. Jiang, M. Bittner, J. A. Hammer III, and W. J. Pavan Mutation of melanosome protein RAB38 in chocolate mice PNAS, April 2, 2002; 99(7): 4471 - 4476. [Abstract] [Full Text] [PDF]

				K. Osanai, M. Iguchi, K. Takahashi, Y. Nambu, T. Sakuma, H. Toga, N. Ohya, H. Shimizu, J. H. Fisher, and D. R. Voelker Expression and Localization of a Novel Rab Small G Protein (Rab38) in the Rat Lung Am. J. Pathol., May 1, 2001; 158(5): 1665 - 1675. [Abstract] [Full Text] [PDF]

				D. Jäger, E. Stockert, A. O. Güre, M. J. Scanlan, J. Karbach, E. Jäger, A. Knuth, L. J. Old, and Y.-T. Chen Identification of a Tissue-specific Putative Transcription Factor in Breast Tissue by Serological Screening of a Breast Cancer Library Cancer Res., March 1, 2001; 61(5): 2055 - 2061. [Abstract] [Full Text]

				K. Kimura, O. Cuvier, and T. Hirano Chromosome Condensation by a Human Condensin Complex in Xenopus Egg Extracts J. Biol. Chem., February 16, 2001; 276(8): 5417 - 5420. [Abstract] [Full Text] [PDF]

				S. K. Loftus, D. M. Larson, L. L. Baxter, A. Antonellis, Y. Chen, X. Wu, Y. Jiang, M. Bittner, J. A. Hammer III, and W. J. Pavan Mutation of melanosome protein RAB38 in chocolate mice PNAS, April 2, 2002; 99(7): 4471 - 4476. [Abstract] [Full Text] [PDF]