| Description | 439 amino acids and 48 kDa in the p64; 454 amino acids in the p67 (15 additional amino acids in N-term; contains from N-term to C-term: a transactivation domain,an acidic domain, a nuclear localization signal, a basic domain, an helix-loop-helix motif, and a leucin zipper; DNA binding protein |
| Expression | expressed in almost all proliferating cells in embryonic and adult tissues; in adult tissues, expression correlates with cell proliferation; abnormally high expression is found in a wide variety of human and rodent tumours |
| Localisation | located predominantly in the nucleus |
| Function | The encoded myc oncoproteins are apparently transcription factors known as basic region-helixloop-helix-leucine zipper (b-HLH-Zip) proteins; like other b-HLH-Zip proteins, they modulate the expression of target genes by binding to specific DNA sequences In this case, however, the binding requires dimerization to another b-HLH-Zip protein, namely Max (the latter can also form heterodimers with Mad as well as homodimers with itself). Myc/Max complexes activate transcription and promote cell proliferation and transformation. Mad/Max complexes, however, repress transcription and block myc-mediated cell transformation. All three complexes bind to the same DNA sequence and are competitors. Expression of c-myc is required for proliferation; it can over-ride p53-induced Gl-arrest by inducing an inhibitor of the cyclin kinase inhibitor WAFI(p2l). The latter (located at 6p2l) normally coordinates S and M phases of the cell cycle. If absent, cells with damaged DNA arrest not in GI but in a G2-like state from which they can pass through additional S phases without intervening normal mitoses (the deformed polyploid cells that result may then die by apoptosis). The uncoupling of S and M may contribute to the acquisition of the chromosomal abnormalities manifested by most tumour cells when apoptotic pathways have been circumvented |
| Homology | the human myc family also includes N-myc and L-myc, rather specifically implicated in neuroblastoma and small-cell lung carcinoma, respectively, in which amplified copy numbers have been found |
| Entity | Burkitt's lymphoma |
| Hybrid/Mutated Gene | the gene is activated by translocation next to an immunoglobulin constant gene. Most frequently, it is positioned near the immunoglobulin heavy-chain (IgH) constant region on chromosome 14 but, in some tumours, near the light-chain region chromosome 2 (IgK) or 22 (IgL). It is now known that immunoglobulin joining enzymes may be involved in recombinations associated with a variety of chromosomal translocations in B and T cells |
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| Entity | amplification has been described in many types of tumour, including breast, cervical and colon cancers, as well as in squamous cell carcinomas of the head and neck, myeloma, non-Hodgkin's lymphoma, gastric adenocarcinomas and ovarian cancer |
| Prognosis | C-myc involvement is by no means universally found in these cancers; there may be a correlation with the more advanced stages, suggesting a value as a prognostic indicator (although this has not been demonstrated in some studies for breast, ovarian and cervical cancers) |
| Oncogenesis | C-myc gene activation (enhanced expression and/or amplification) may result from chromosomal duplication as well as translocation, and from retroviral as well as point mutation. Multiple copies of the gene may be evidenced in homogeneously staining chromosomal regions and in double minutes |
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| Entity | Role of c-myc in other conditions |
| Disease | In adult respiratory distress syndrome the degree of diffuse alveolar damage and consequently the prognosis may be related to the intensity of expression of c-myc in the alveolar cells which, if severe, may contribute to deregulation of cellular proliferation and apoptosis. In endometriosis, c-myc expression is a possibly important regulator of cellular proliferation. |
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| c-myc and immunoglobulin kappa light chain constant genes are on the 8q+ chromosome of three Burkitt lymphoma lines with t(2;8) translocations. |
| Rappold GA, Hameister H, Cremer T, Adolph S, Henglein B, Freese UK, Lenoire GM, Bornkamm GW |
| The EMBO journal. 1984 ; 3 (12) : 2951-2955. |
| PMID 6441706 |
| |
| Amplification of the c-myc oncogene in a subpopulation of human small cell lung cancer. |
| Saksela K, Bergh J, Lehto VP, Nilsson K, Alitalo K |
| Cancer research. 1985 ; 45 (4) : 1823-1827. |
| PMID 2983887 |
| |
| Myc family genes: a dispersed multi-gene family. |
| Depinho RA, Hatton K, Ferrier P, Zimmerman K, Legouy E, Tesfaye A, Collum R, Yancopoulos G, Nisen P, Alt F |
| Annals of clinical research. 1986 ; 18 (5-6) : 284-289. |
| PMID 3551773 |
| |
| c-myc protooncogene polypeptide expression in endometriosis. |
| Schenken RS, Johnson JV, Riehl RM |
| American journal of obstetrics and gynecology. 1991 ; 164 (4) : 1031-1036. |
| PMID 1707594 |
| |
| The c-myc oncogene in tumor progression. |
| Garte SJ |
| Critical reviews in oncogenesis. 1993 ; 4 (4) : 435-449. |
| PMID 8353142 |
| |
| Chromosomal translocations deregulating c-myc are associated with normal immune responses. |
| Roschke V, Kopantzev E, Dertzbaugh M, Rudikoff S |
| Oncogene. 1997 ; 14 (25) : 3011-3016. |
| PMID 9223664 |
| |
| Repression by the Mad(Mxi1)-Sin3 complex. |
| Schreiber-Agus N, DePinho RA |
| BioEssays : news and reviews in molecular, cellular and developmental biology. 1998 ; 20 (10) : 808-818. |
| PMID 9819568 |
| |
| Amplification of the c-myc oncogene in non-small cell lung cancer. |
| Ozkara HA, Ozkara S, Topˆßu S, Criss WE |
| Tumori. 1999 ; 85 (6) : 508-511. |
| PMID 10774575 |
| |
| MYC oncogenes and human neoplastic disease. |
| Nesbit CE, Tersak JM, Prochownik EV |
| Oncogene. 1999 ; 18 (19) : 3004-3016. |
| PMID 10378696 |
| |
| Proliferation, C-myc, and cyclin D1 expression in diffuse alveolar damage: potential roles in pathogenesis and implications for prognosis. |
| Adamson A, Perkins S, Brambilla E, Tripp S, Holden J, Travis W, Guinee D Jr |
| Human pathology. 1999 ; 30 (9) : 1050-1057. |
| PMID 10492039 |
| |
