Download Gene Section MYC (v-myc myelocytomatosis viral oncogene

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Gene Section
Mini Review
MYC (v-myc myelocytomatosis viral oncogene
homolog (avian))
Niels B Atkin
Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex, UK (NBA)
Published in Atlas Database: August 2000
Online updated version : http://AtlasGeneticsOncology.org/Genes/MYCID27.html
DOI: 10.4267/2042/37661
This article is an update of : Larizza L, Beghini A. KIT. Atlas Genet Cytogenet Oncol Haematol 1999;3(1):1-3
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2000 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
Protein
Other names: C-MYC. Identified as the oncogene of
the MC29 avian myelocytomatosis virus
HGNC (Hugo): MYC
Location: 8q24
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-helixloophelix-leucine zipper (b-HLH-Zip) proteins; like other bHLH-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.
c-MYC (8q24) in normal cells: PAC 944B18 (top) and PAC
968N11 (below) - Courtesy Mariano Rocchi, Resources for
Molecular Cytogenetics.
DNA/RNA
Transcription
Alternative splicing; coding sequences: 1318 and 1362
bp for proteins p64 and p67 respectively.
Atlas Genet Cytogenet Oncol Haematol. 2000; 4(4)
181
MYC (v-myc myelocytomatosis viral oncogene homolog (avian))
Atkin NB
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.
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.
To be noted
Note
Although c-myc appears to be active in variety of
tumours, it is important to realise that in common with
other mechanistic pathways to cancer induction and
progression no single genetic event (including c-myc
deregulation) will prove to be necessary in the light of
the inherent complexity and diversity of cellular
pathways leading to neoplasia.
Homology
The human myc family also includes N-myc and Lmyc, rather specifically implicated in neuroblastoma
and small-cell lung carcinoma, respectively, in which
amplified copy numbers have been found.
References
Implicated in
Rappold GA, Hameister H, Cremer T, Adolph S, Henglein B,
Freese UK, Lenoire GM, Bornkamm GW. c-myc and
immunoglobulin kappa light chain constant genes are on the
8q+ chromosome of three Burkitt lymphoma lines with t(2;8)
translocations. EMBO J. 1984 Dec 1;3(12):2951-5
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.
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.
Saksela K, Bergh J, Lehto VP, Nilsson K, Alitalo K.
Amplification of the c-myc oncogene in a subpopulation of
human small cell lung cancer. Cancer Res. 1985
Apr;45(4):1823-7
Depinho RA, Hatton K, Ferrier P, Zimmerman K, Legouy E,
Tesfaye A, Collum R, Yancopoulos G, Nisen P, Alt F. Myc
family genes: a dispersed multi-gene family. Ann Clin Res.
1986;18(5-6):284-9
Schenken RS, Johnson JV, Riehl RM. c-myc protooncogene
polypeptide expression in endometriosis. Am J Obstet
Gynecol. 1991 Apr;164(4):1031-6; discussion 1036-7
Garte SJ. The c-myc oncogene in tumor progression. Crit Rev
Oncog. 1993;4(4):435-49
Roschke V, Kopantzev E, Dertzbaugh M, Rudikoff S.
Chromosomal translocations deregulating c-myc
are
associated with normal immune responses. Oncogene. 1997
Jun 26;14(25):3011-6
Schreiber-Agus N, DePinho RA. Repression by the Mad(Mxi1)Sin3 complex. Bioessays. 1998 Oct;20(10):808-18
Adamson A, Perkins S, Brambilla E, Tripp S, Holden J, Travis
W, Guinee D Jr. Proliferation, C-myc, and cyclin D1 expression
in diffuse alveolar damage: potential roles in pathogenesis and
implications for prognosis. Hum Pathol. 1999 Sep;30(9):1050-7
Nesbit CE, Tersak JM, Prochownik EV. MYC oncogenes and
human
neoplastic
disease.
Oncogene.
1999
May
13;18(19):3004-16
Ozkara HA, Ozkara S, Topçu S, Criss WE. Amplification of the
c-myc oncogene in non-small cell lung cancer. Tumori. 1999
Nov-Dec;85(6):508-11
This article should be referenced as such:
Role of c-myc in other conditions
Atkin NB. MYC (v-myc myelocytomatosis viral oncogene
homolog (avian)). Atlas Genet Cytogenet Oncol Haematol.
2000; 4(4):181-182.
Disease
Atlas Genet Cytogenet Oncol Haematol. 2000; 4(4)
182