Abstract
We have determined the nucleotide sequence and transforming activity of the human L-myc gene and a processed L-myc pseudogene (L-myc psi). We demonstrate by cotransformation assays that a 10.6-kb EcoRI fragment derived from a human placental library contains a complete and functional L-myc gene including transcriptional regulatory sequences sufficient for expression in rat embryo fibroblasts. Organization of the L-myc gene was determined by comparing its sequence to those of the L-myc psi gene and an L-myc cDNA clone derived from a human small cell lung carcinoma. Our results show that L-myc has a three-exon organization similar to that of the c-myc and N-myc genes. The putative L-myc gene product consists of 364 amino acids and contains five of the seven homology regions highly conserved between c-myc and N-myc. These conserved regions are located along the entire length of the putative L-myc protein and are interspersed among nonconserved regions. While the putative L-myc gene product is of a smaller size when compared to the c- and N-myc proteins, the relative positions of certain conserved residues occur in corresponding locations along the peptide backbone of the three proteins. In addition, comparison of the human and murine L-myc gene sequences indicate that the relatively large 5' and 3' untranslated regions are evolutionarily conserved, but that these sequences are totally divergent between the L-, c-, and N-myc genes. Finally, we demonstrate that, like the N- and c-myc genes, the L-myc gene can cooperate with a mutant Ha-ras gene to cause malignant transformation of rat embryo fibroblasts in culture. Our analyses clearly prove that L-myc represents a functional member of the myc oncogene family and further delineate structural features that may be important for the common and divergent functions of the members of this gene family.
References
57
Referenced
80
10.1016/0092-8674(82)90159-3
10.1038/318533a0
10.1038/306274a0
10.1101/SQB.1986.051.01.106
- Alt, F., E. Harlow, and E. Ziff. 1987. Nuclear oncogenes. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, (In press).
10.1016/0092-8674(79)90188-0
10.1016/0092-8674(83)90534-2
10.1002/j.1460-2075.1983.tb01749.x
/ EMBO J. / Sequence of the murine and human cellular myc oncogenes and two modes of myc transcription resulting from chromosome translocation in B lymphoid tumours. (1983)10.1016/0092-8674(86)90509-X
10.1038/320760a0
{'key': '2021111319444646000_1.10.1311.11', 'first-page': '2905', 'article-title': 'Molecular basis of heavy-chain class switching and switch region deletion in an Abelson virus-transformed cell line.', 'volume': '4', 'year': '1985', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Molecular basis of heavy-chain class switching and switch region deletion in an Abelson virus-transformed cell line. (1985)10.1073/pnas.83.6.1827
10.1002/jcb.240330404
10.1038/322748a0
10.1038/296262a0
{'key': '2021111319444646000_1.10.1311.16', 'first-page': '173', 'article-title': 'Sequence and structure of the coding region of the human H-ras-1 gene from T24 bladder carcinoma cells.', 'volume': '2', 'year': '1983', 'journal-title': 'J. Mol. Appl. Genet.'}
/ J. Mol. Appl. Genet. / Sequence and structure of the coding region of the human H-ras-1 gene from T24 bladder carcinoma cells. (1983)10.1016/0092-8674(83)90535-4
{'key': '2021111319444646000_1.10.1311.18', 'first-page': '2486', 'article-title': 'Proteins encoded by the human c-myc oncogene: Differential expression in neoplastic cells.', 'volume': '4', 'year': '1984', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Proteins encoded by the human c-myc oncogene: Differential expression in neoplastic cells. (1984)10.1073/pnas.78.6.3824
10.1073/pnas.83.16.5929
10.1038/318188a0
10.1016/0092-8674(84)90012-6
{'key': '2021111319444646000_1.10.1311.23', 'first-page': '7', 'article-title': 'Tumorigenicity of fibroblast lines expressing the adenovirus E1A, cellular p53, and normal c-myc genes.', 'volume': '6', 'year': '1986', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Tumorigenicity of fibroblast lines expressing the adenovirus E1A, cellular p53, and normal c-myc genes. (1986){'key': '2021111319444646000_1.10.1311.24', 'first-page': '327', 'article-title': 'The regulation and expression of c-myc in normal and malignant cells.', 'volume': '4', 'year': '1986', 'journal-title': 'Annu. Rev. Immunol.'}
/ Annu. Rev. Immunol. / The regulation and expression of c-myc in normal and malignant cells. (1986){'key': '2021111319444646000_1.10.1311.25', 'first-page': '4499', 'article-title': 'Expression of the c-myc proto-oncogene during development of Xenopus laevis.', 'volume': '6', 'year': '1986', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Expression of the c-myc proto-oncogene during development of Xenopus laevis. (1986)10.1016/0092-8674(83)90169-1
10.1038/319073a0
10.1073/pnas.83.17.6480
10.1038/304596a0
-
Legouy, E., DePinho, R.A. Zimmerman, K. Collum, R. Yancopoulos, G.D. Mitsock, L. Kriz, R. and Alt. F.W. 1987. Structure and expression of the murine L-myc gene. EMBO J., (In press).
(
10.1002/j.1460-2075.1987.tb02657.x
) 10.1101/SQB.1986.051.01.098
10.1073/pnas.81.18.5758
10.1093/nar/10.2.459
10.1038/318069a0
{'key': '2021111319444646000_1.10.1311.35', 'first-page': '6217', 'article-title': 'Enhanced expression of the N-myc gene in Wilms tumors.', 'volume': '46', 'year': '1986', 'journal-title': 'Cancer Res.'}
/ Cancer Res. / Enhanced expression of the N-myc gene in Wilms tumors. (1986)10.1126/science.6463648
{'key': '2021111319444646000_1.10.1311.37', 'first-page': '942', 'article-title': 'Multiple growth associated nuclear proteins immunoprecipitated by antisera raised against human c-myc peptide antigens.', 'volume': '6', 'year': '1986', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Multiple growth associated nuclear proteins immunoprecipitated by antisera raised against human c-myc peptide antigens. (1986)10.1038/263211a0
10.1038/306803a0
{'key': '2021111319444646000_1.10.1311.40', 'first-page': '7742', 'article-title': 'The protein encoded by the human proto-oncogene c-myc. Proc. Natl. Acad. Sci.', 'year': '1984', 'journal-title': '81'}
/ 81 / The protein encoded by the human proto-oncogene c-myc. Proc. Natl. Acad. Sci. (1984)10.1038/304602a0
{'key': '2021111319444646000_1.10.1311.42', 'first-page': '481', 'article-title': 'Avian myelocytomatosis virus myc and adenovirus early region 1A promote the in vitro establishment of cultured primary cells.', 'volume': '2', 'year': '1984', 'journal-title': 'Cancer cells'}
/ Cancer cells / Avian myelocytomatosis virus myc and adenovirus early region 1A promote the in vitro establishment of cultured primary cells. (1984)10.1016/0092-8674(84)90406-9
10.1038/305245a0
10.1038/316160a0
10.1128/jvi.31.2.514-521.1979
/ J. Virol. / DNA and RNA from uninfected vertebrate cells contain nucleotide sequences related to the putative transforming gene of avian myelocytoma- tosis virus. (1979)10.1126/science.3008339
10.1038/310469a0
{'key': '2021111319444646000_1.10.1311.49', 'first-page': '5', 'article-title': 'The v- and c-myc proteins colocalize in situ with small nuclear ribonu- cleoprotein particles.', 'volume': '1', 'year': '1987', 'journal-title': 'Oncogene'}
/ Oncogene / The v- and c-myc proteins colocalize in situ with small nuclear ribonu- cleoprotein particles. (1987)10.1073/pnas.83.6.1772
{'key': '2021111319444646000_1.10.1311.51', 'first-page': '1697', 'article-title': 'Definition of regions in human c-myc involved in transformation and nuclear local- ization.', 'volume': '7', 'year': '1987', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Definition of regions in human c-myc involved in transformation and nuclear local- ization. (1987)10.1073/pnas.83.11.3698
10.1016/0167-4781(84)90057-5
/ Biochim. Biophys. Acta / Processed pseudogenes: Characteristics and evolution. (1984){'key': '2021111319444646000_1.10.1311.54', 'first-page': '448', 'article-title': 'Expression and characterization of the human c-myc DNA-binding protein.', 'volume': '5', 'year': '1985', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Expression and characterization of the human c-myc DNA-binding protein. (1985)10.1126/science.2997917
10.1073/pnas.82.16.5455
10.1038/319780a0
Dates
Type | When |
---|---|
Created | 18 years, 2 months ago (June 5, 2007, 5:15 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 13, 2021, 10:45 p.m.) |
Indexed | 1 year, 7 months ago (Jan. 27, 2024, 5:36 a.m.) |
Issued | 37 years, 8 months ago (Dec. 1, 1987) |
Published | 37 years, 8 months ago (Dec. 1, 1987) |
Published Online | 37 years, 8 months ago (Dec. 1, 1987) |
Published Print | 37 years, 8 months ago (Dec. 1, 1987) |
@article{DePinho_1987, title={The human myc gene family: structure and activity of L-myc and an L-myc pseudogene.}, volume={1}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1.10.1311}, DOI={10.1101/gad.1.10.1311}, number={10}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={DePinho, R A and Hatton, K S and Tesfaye, A and Yancopoulos, G D and Alt, F W}, year={1987}, month=dec, pages={1311–1326} }