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Gene Review

Cited1  -  Cbp/p300-interacting transactivator with...

Mus musculus

Synonyms: AI316840, AU019144, Cbp/p300-interacting transactivator 1, Melanocyte-specific protein 1, Msg1
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Disease relevance of Cited1

  • Here we report that mice with melanocyte-specific expression of activated H-rasG12V on an ink4a-deficient background develop spontaneous cutaneous melanomas after a short latency and with high penetrance [1].
  • This promoter fragment activates transcription of a reporter gene in pigmented melanoma cells, but not in amelanotic melanoma cells or nonmelanocytic cells, indicating that Msg1 expression is at least partially regulated at the transcriptional level [2].
  • Notably, MDA-MB-435 cells also expressed melanocyte-specific proteins as did another highly aggressive breast cancer cell line [3].
  • Since the adenovirus E1A products have proved a useful tool for understanding control of differentiation in other systems, we explored the possibility of using E1A as a probe for factors controlling melanocyte-specific gene expression and differentiation [4].
  • CONCLUSIONS: Our results demonstrate that DC-based genetic immunization of mice with TRP2, a clinically relevant melanocyte-specific self-antigen, induces effective cellular immunity and prevents metastatic growth of B16 melanoma cells in vivo [5].

High impact information on Cited1

  • These findings indicate that melanocyte-specific factors present before neoplastic transformation can have a pivotal role in governing melanoma progression [6].
  • To further elucidate the mutant phenotype, we studied the expression of melanocyte specific genes in the skin of Light mice [7].
  • The study of Mitf has provided many insights into the biology of melanocytes and helped to explain how melanocyte-specific gene expression and signaling is regulated [8].
  • We have cloned and sequenced mouse cDNAs corresponding to a third member of a family of melanocyte-specific mRNAs, which encode tyrosinase and related proteins [9].
  • Tyrosinase is a melanocyte-specific enzyme critical for the synthesis of melanin, a process normally restricted to a post-Golgi compartment termed the melanosome [10].

Biological context of Cited1


Anatomical context of Cited1


Associations of Cited1 with chemical compounds

  • The melanocyte-specific glycoprotein Pmel17 is enriched in the lumen of premelanosomes, where it associates with characteristic striations of unknown composition upon which melanin is deposited [17].
  • Dopachrome tautomerase (DT) (EC is a melanocyte-specific, membrane-associated, heat-labile, non-dialyzable, protease-sensitive factor which catalyzes the isomeric rearrangement of dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA), apparently through a tautomerization reaction [18].
  • Here, we generated and characterized mice harboring a 4-hydroxytamoxifen (OHT)-inducible Cre recombinase-estrogen receptor fusion transgene under the control of the melanocyte-specific tyrosinase promoter, designated Tyr::CreER(T2) [19].
  • These cell lines show characteristic phenotypes of transformed melanocytes, and express Grm1, and Grm5 (another metabotropic glutamate receptor), as well as melanocyte-specific protein markers [20].
  • Although most cytotoxic chemicals were nonspecific in this primary screen (i.e. killing both Mel-Ab and HT-1080 cells), several of the compounds tested exhibited high melanocyte-specific cytotoxicity, similar to HQ and 4-S-CAP [21].

Other interactions of Cited1


Analytical, diagnostic and therapeutic context of Cited1

  • While Cited1 also binds to the TGFbeta signal transducer Smad4, this has not been shown for Cited2 [26].
  • MDA-MB-435 xenograft tissue sections stained entirely positive for epithelium-specific markers but only partially positive for melanocyte-specific markers [3].
  • We further focused on a sequence located at -15 kb, which we identified as a melanocyte-specific enhancer as shown by cell culture and transgenic mice experiments [27].
  • Sequence analysis revealed that this clone represents a novel gene, encoding a putative transmembrane glycoprotein which showed the highest homology to the precursor of pMEL17, a melanocyte-specific protein. nmb RNA expression was absent in most tumor-cell lines tested and not restricted to the melanocytic lineage [28].
  • BACKGROUND: The induction of cellular immune responses to melanocyte-specific enzymes such as the tyrosinase family of proteins is the goal of various clinical studies for the immunotherapy of melanoma [5].


  1. Cooperative effects of INK4a and ras in melanoma susceptibility in vivo. Chin, L., Pomerantz, J., Polsky, D., Jacobson, M., Cohen, C., Cordon-Cardo, C., Horner, J.W., DePinho, R.A. Genes Dev. (1997) [Pubmed]
  2. MSG1 (melanocyte-specific gene 1): mapping to chromosome Xq13.1, genomic organization, and promoter analysis. Fenner, M.H., Parrish, J.E., Boyd, Y., Reed, V., MacDonald, M., Nelson, D.L., Isselbacher, K.J., Shioda, T. Genomics (1998) [Pubmed]
  3. Lineage infidelity of MDA-MB-435 cells: expression of melanocyte proteins in a breast cancer cell line. Sellappan, S., Grijalva, R., Zhou, X., Yang, W., Eli, M.B., Mills, G.B., Yu, D. Cancer Res. (2004) [Pubmed]
  4. The Microphthalmia gene product interacts with the retinoblastoma protein in vitro and is a target for deregulation of melanocyte-specific transcription. Yavuzer, U., Keenan, E., Lowings, P., Vachtenheim, J., Currie, G., Goding, C.R. Oncogene (1995) [Pubmed]
  5. Dendritic cell-based genetic immunization in mice with a recombinant adenovirus encoding murine TRP2 induces effective anti-melanoma immunity. Tüting, T., Steitz, J., Brück, J., Gambotto, A., Steinbrink, K., DeLeo, A.B., Robbins, P., Knop, J., Enk, A.H. The journal of gene medicine. (1999) [Pubmed]
  6. The melanocyte differentiation program predisposes to metastasis after neoplastic transformation. Gupta, P.B., Kuperwasser, C., Brunet, J.P., Ramaswamy, S., Kuo, W.L., Gray, J.W., Naber, S.P., Weinberg, R.A. Nat. Genet. (2005) [Pubmed]
  7. Light is a dominant mouse mutation resulting in premature cell death. Johnson, R., Jackson, I.J. Nat. Genet. (1992) [Pubmed]
  8. Melanocytes and the microphthalmia transcription factor network. Steingrímsson, E., Copeland, N.G., Jenkins, N.A. Annu. Rev. Genet. (2004) [Pubmed]
  9. A second tyrosinase-related protein, TRP-2, maps to and is mutated at the mouse slaty locus. Jackson, I.J., Chambers, D.M., Tsukamoto, K., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Hearing, V. EMBO J. (1992) [Pubmed]
  10. Endoplasmic reticulum retention is a common defect associated with tyrosinase-negative albinism. Halaban, R., Svedine, S., Cheng, E., Smicun, Y., Aron, R., Hebert, D.N. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  11. Cited1 is required in trophoblasts for placental development and for embryo growth and survival. Rodriguez, T.A., Sparrow, D.B., Scott, A.N., Withington, S.L., Preis, J.I., Michalicek, J., Clements, M., Tsang, T.E., Shioda, T., Beddington, R.S., Dunwoodie, S.L. Mol. Cell. Biol. (2004) [Pubmed]
  12. Msg1 and Mrg1, founding members of a gene family, show distinct patterns of gene expression during mouse embryogenesis. Dunwoodie, S.L., Rodriguez, T.A., Beddington, R.S. Mech. Dev. (1998) [Pubmed]
  13. Brachyury-related transcription factor Tbx2 and repression of the melanocyte-specific TRP-1 promoter. Carreira, S., Dexter, T.J., Yavuzer, U., Easty, D.J., Goding, C.R. Mol. Cell. Biol. (1998) [Pubmed]
  14. Functional gene expression analysis uncovers phenotypic switch in aggressive uveal melanomas. Onken, M.D., Ehlers, J.P., Worley, L.A., Makita, J., Yokota, Y., Harbour, J.W. Cancer Res. (2006) [Pubmed]
  15. Role of microphthalmia transcription factor (Mitf) in melanoma differentiation. Lekmine, F., Chang, C.K., Sethakorn, N., Das Gupta, T.K., Salti, G.I. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  16. Peptide-specific cytotoxic T lymphocytes restricted by nonself major histocompatibility complex class I molecules: reagents for tumor immunotherapy. Sadovnikova, E., Stauss, H.J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  17. Pmel17 initiates premelanosome morphogenesis within multivesicular bodies. Berson, J.F., Harper, D.C., Tenza, D., Raposo, G., Marks, M.S. Mol. Biol. Cell (2001) [Pubmed]
  18. Evidence that dopachrome tautomerase is a ferrous iron-binding glycoprotein. Chakraborty, A.K., Orlow, S.J., Pawelek, J.M. FEBS Lett. (1992) [Pubmed]
  19. Characterization of melanocyte-specific inducible Cre recombinase transgenic mice. Bosenberg, M., Muthusamy, V., Curley, D.P., Wang, Z., Hobbs, C., Nelson, B., Nogueira, C., Horner, J.W., Depinho, R., Chin, L. Genesis (2006) [Pubmed]
  20. Grm5 expression is not required for the oncogenic role of Grm1 in melanocytes. Marín, Y.E., Namkoong, J., Shin, S.S., Raines, J., Degenhardt, K., White, E., Chen, S. Neuropharmacology (2005) [Pubmed]
  21. Development of an in vitro primary screen for skin depigmentation and antimelanoma agents. Dooley, T.P., Gadwood, R.C., Kilgore, K., Thomasco, L.M. Skin Pharmacol. (1994) [Pubmed]
  22. MRG1, the product of a melanocyte-specific gene related gene, is a cytokine-inducible transcription factor with transformation activity. Sun, H.B., Zhu, Y.X., Yin, T., Sledge, G., Yang, Y.C. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  23. Dual inactivation of RB and p53 pathways in RAS-induced melanomas. Bardeesy, N., Bastian, B.C., Hezel, A., Pinkel, D., DePinho, R.A., Chin, L. Mol. Cell. Biol. (2001) [Pubmed]
  24. Pax3 and regulation of the melanocyte-specific tyrosinase-related protein-1 promoter. Galibert, M.D., Yavuzer, U., Dexter, T.J., Goding, C.R. J. Biol. Chem. (1999) [Pubmed]
  25. Coordinate extinction of melanocyte-specific gene expression in hybrid cells. Powers, T.P., Davidson, R.L. Somat. Cell Mol. Genet. (1996) [Pubmed]
  26. Expression analysis of the chicken homologue of CITED2 during early stages of embryonic development. Schlange, T., Andrée, B., Arnold, H., Brand, T. Mech. Dev. (2000) [Pubmed]
  27. A conserved transcriptional enhancer that specifies Tyrp1 expression to melanocytes. Murisier, F., Guichard, S., Beermann, F. Dev. Biol. (2006) [Pubmed]
  28. nmb, a novel gene, is expressed in low-metastatic human melanoma cell lines and xenografts. Weterman, M.A., Ajubi, N., van Dinter, I.M., Degen, W.G., van Muijen, G.N., Ruitter, D.J., Bloemers, H.P. Int. J. Cancer (1995) [Pubmed]
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