Myc

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V-myc myelocytomatosis viral oncogene homolog (avian)
Image:PBB Protein MYC image.jpg
PDB rendering based on 1nkp.
Identifiers
Symbol(s)	MYC; c-Myc
External IDs	OMIM: 190080 MGI: 97250 Homologene: 31092
Gene ontology Molecular Function: • transcription factor activity • protein binding Cellular Component: • nucleus • spindle Biological Process: • release of cytochrome c from mitochondria • DNA fragmentation during apoptosis • regulation of transcription, DNA-dependent • regulation of transcription from RNA polymerase II promoter • cellular iron ion homeostasis • caspase activation • cell cycle arrest • positive regulation of cell proliferation • induction of apoptosis by intracellular signals • activation of pro-apoptotic gene products • negative regulation of survival gene product activity • response to radiation • regulation of apoptosis
Orthologs
	Human	Mouse
Entrez	4609	17869
Ensembl	na	ENSMUSG00000022346
Uniprot	na	O88594
Refseq	XM_001129632 (mRNA) XP_001129632 (protein)	NM_010849 (mRNA) NP_034979 (protein)
Location	na	Chr 15: 61.82 - 61.82 Mb
Pubmed search	[1]	[2]

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Powerpoint slides on Myc Images of Myc Photos of Myc Podcasts & MP3s on Myc Videos on Myc
Evidence Based Medicine
Cochrane Collaboration on Myc Bandolier on Myc TRIP on Myc
Clinical Trials
Ongoing Trials on Myc at Clinical Trials.gov Trial results on Myc Clinical Trials on Myc at Google
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US National Guidelines Clearinghouse on Myc NICE Guidance on Myc NHS PRODIGY Guidance FDA on Myc CDC on Myc
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News
Myc in the news Be alerted to news on Myc News trends on Myc
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Definitions of Myc
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Patient resources on Myc Discussion groups on Myc Patient Handouts on Myc Directions to Hospitals Treating Myc Risk calculators and risk factors for Myc
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Myc en Espanol Myc en Francais
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Overview

Myc (cMyc) is a protooncogene, which is overexpressed in a wide range of human cancers. When it is specifically-mutated, or overexpressed, it increases cell proliferation and functions as an oncogene. Myc gene encodes for a transcription factor that regulates expression of 15% of all genes ^[1] through binding on Enhancer Box sequences (E-boxes) and recruiting histone acetyltransferases (HATs). Myc belongs to Myc family of transcription factors, which also includes N-Myc and L-Myc genes. Myc-family transcription factors contain the bHLH/LZ (basic Helix-Loop-Helix Leucine Zipper) domain.

Discovery

Myc gene was first discovered in Burkitt's lymphoma patients. In Burkitt's lymphoma, cancer cells show chromosomal translocations, in which Chromosome 8 is frequently involved. Cloning the break point of the fusion chromosomes revealed a gene that was similar to myelocytomatosis viral oncogene (v-Myc). Thus, the newfound cellular gene was named c-Myc.

Structure

Myc belongs to Myc family of transcription factors, which also includes N-Myc and L-Myc genes. Myc family of transcription factors contain bHLH/LZ (basic Helix-Loop-Helix Leucine Zipper) domain. Myc protein, through its bHLH domain can bind to DNA, while the leucine zipper domain allows the dimerisation with its partner Max, another bHLH transcription factor.

Molecular Function

Myc protein is a transcription factor that activates expression of a great number of genes through binding on consensus sequences (Enhancer Box sequences (E-boxes)) and recruiting histone acetyltransferases (HATs). It can also act as a transcriptional repressor. By binding Miz-1 transcription factor and displacing the p300 co-activator, it inhibits expression of Miz-1 target genes.

Myc is activated upon various mitogenic signals such as Wnt, Shh and EGF (via the MAPK/ERK pathway). By modifying the expression of its target genes, Myc activation results in numerous biological effects. The first to be discovered was its capability to drive cell proliferation (upregulates cyclins, downregulates p21), but it also plays a very important role in regulating cell growth (upregulates ribosomal RNA and proteins), apoptosis (upregulates Bcl-2), differentiation and stem cell self-renewal. Myc is a very strong proto-oncogene and it is very often found to be upregulated in many types of cancers.

Animal Models

During the discovery of Myc gene, it was realized that chromosomes that translocate to Chromosome 8 contained immunoglobulin genes at the break point. Enhancers that normally drive expression of immunoglobin genes, now lead to overexpression of Myc proto-oncogene in lymphoma cells. To study the mechanism of tumorigenesis in Burkitt's lymphoma by mimicking expression pattern of Myc in these cancer cells, transgenic mouse models were developed. Myc gene placed under the control of IgM heavy chain enhancer in transgenic mice gives rise to mainly lymphomas. Later on, to study effects of Myc in other types of cancer, transgenic mice that overexpress Myc in different tissues (liver, breast) were also made. In all these mouse models overexpression of Myc causes tumorigenesis, illustrating the potency of Myc oncogene.

References

Further reading

External links

• The Myc Protein
• Myc antibody review
• NCBI Human Myc protein
• http://www.myccancergene.org
• http://med.stanford.edu/labs/dean_felsher Felsher Lab, Stanford University, California
• http://www.bioscience.org/knockout/ref/davis.htm
• MeSH myc+Proto-Oncogene+Proteins

v • d • e Oncogenes/Proto-oncogenes
Transcription factors	AP-1 (c-Fos, c-Jun) - c-Myc
Tyrosine kinase / Receptors	c-ErbB (HER2/neu, Her 3) - c-Kit - c-Met - c-Ret - Flt3 -
Other	c-Akt - c-Bcl-2 - c-Mdm2 - -c-Raf - c-Ras (HRAS) - c-Sis - c-Src - Notch - Stathmin

v • d • e Transcription factors and intracellular receptors
(1) Basic domains	(1.1) Basic leucine zipper (bZIP) Activating transcription factor (1, 2, 3, 4, 5, 6) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3) • GABPA • MAF (B, F, G, K) • NRL • NRF1 • XBP1 (1.2) Basic helix-loop-helix (bHLH) ATOH1 • AhR • AHRR • ARNT • ASCL1 • BMAL (ARNTL, ARNTL2) • CLOCK • HIF (1A, 3A) • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • NEUROD1 • Twist • USF1 (1.3) bHLH-ZIP Myc • MITF • SREBP (1, 2) (1.6) Basic helix-span-helix (bHSH) AP-2
(2) Zinc finger DNA-binding domains	(2.1) Nuclear receptor (Cys4) subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR) • subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX) • subfamily 3 (Steroid hormone (Estrogen (α, β), Estrogen related (α, β, γ), Androgen, Glucocorticoid, Mineralocorticoid, Progesterone)) • subfamily 4 NUR (NGFIB, NOR1, NURR1) • subfamily 5 (LRH-1, SF1) • subfamily 6 (GCNF) • subfamily 0 (DAX1, SHP) (2.2) Other Cys4 GATA (1, 2, 3, 4, 5, 6) (2.3) Cys2His2 General transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH: 1, 2) • GLI-Krüppel family (1, 2, 3, YY1) • KLF (2, 4, 5, 6, 10, 11, 12, 13) • Sp1 • zinc finger (3, 35, 43, 146, 148, 165, 217, 268, 281, 350) • Zbtb7 (7A) • ZBT (16, 17, 33) (2.4) Cys6 HIVEP1
(3) Helix-turn-helix domains	(3.1) Homeo domain ARX • Homeobox (A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C6, C8, C9, C13, D1, D3, D4, D9, D10, D11, D12, D13) • NANOG • NKX (2-1, 2-5, 3-1) • POU domain (PIT-1, BRN-3: 1, 2, Octamer transcription factor: 1, 2, 3/4, 6, 7) (3.2) Paired box PAX (1, 2, 3, 4, 5, 6, 7, 8, 9) (3.3) Fork head / winged helix E2F (1, 2, 3, 4, 5) • FOX proteins (C1, C2, E1, G1, H1, L2, M1, N3, O3, O4, P1, P2, P3) (3.4) Heat Shock Factors HSF1 (3.5) Tryptophan clusters ELF (4, 5) • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB (3.6) TEA domain transcriptional enhancer factor 1, 2
(4) β-Scaffold factors with minor groove contacts	(4.1) Rel homology region NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (5, C1, C2, C3, C4) (4.2) STAT STAT (1, 2, 3, 4, 5, 6) (4.3) p53 p53 (4.4) MADS box Mef2 (A, B, C, D) • SRF (4.7) High mobility group HNF (1A, 1B) • LEF1 • SOX (3, 4, 6, 9, 10, 13, 18) • SRY • SSRP1 (4.10) Cold-shock domain CSDA
(0) Other transcription factors	(0.2) HMGI(Y) HMGA (1, 2) (0.3) Pocket domain Rb • RBL1 • RBL2 (0.6) Miscellaneous ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • Rho/Sigma • R-SMAD

v • d • e WikiDoc Research Resources for Myc
Articles on Myc	Most recent articles on Myc • Most cited articles on Myc • Review articles on Myc • Articles on Myc in N Eng J Med, Lancet, BMJ
Media (Slides, Video, Images, MP3) on Myc	Powerpoint slides on Myc • Images of Myc • Photos of Myc • Podcasts & MP3s on Myc • Videos on Myc
Evidence Based Medicine Regarding Myc	Cochrane Collaboration on Myc • Bandolier on Myc • TRIP on Myc
Cost Effectiveness of Myc	Cost Effectiveness of Myc
Clinical Trials Involving Myc	Ongoing Trials on Myc at Clinical Trials.gov • Trial results on Myc • Clinical Trials on Myc at Google
Guidelines / Policies / Government Resources (FDA/CDC) Regarding Myc	US National Guidelines Clearinghouse on Myc • NICE Guidance on Myc • NHS PRODIGY Guidance • FDA on Myc • CDC on Myc
Textbook Information on Myc	Books and Textbook Information on Myc
Pharmacology Resources on Myc	Dosing of Myc • Drug interactions with Myc • Side effects of Myc • Allergic reactions to Myc • Overdose information on Myc • Carcinogenicity information on Myc • Myc in pregnancy • Pharmacokinetics of Myc •
Genetics, Pharmacogenomics, and Proteinomics of Myc	Genetics of Myc • Pharmacogenomics of Myc • Proteomics of Myc
Newstories on Myc	Myc in the news • Be alerted to news on Myc • News trends on Myc
Commentary on Myc	Blogs on Myc
Patient Resources on Myc	Patient resources on Myc • Discussion groups on Myc • Patient Handouts on Myc • Directions to Hospitals Treating Myc • Risk calculators and risk factors for Myc
Healthcare Provider Resources on Myc	Symptoms of Myc • Causes & Risk Factors for Myc • Diagnostic studies for Myc • Treatment of Myc
Continuing Medical Education (CME) Programs on Myc	CME Programs on Myc
International Resources on Myc	Myc en Espanol • Myc en Francais
Business Resources on Myc	Myc in the Marketplace • Patents on Myc
Informatics Resources on Myc	List of terms related to Myc