Proteopedia - User contributions [en]

Kwon sandbox

2009-11-03T16:00:42Z

Jason Kwon:

<applet load='2A93-custom.pdb' size='400' frame='true' align='right' caption='c-Myc is a [http://en.wikipedia.org/wiki/DNA-binding_protein DNA binding protein]' scene='C-Myc/Custom/2'/>

== Introduction ==

----

<scene name='Kwon_sandbox/C-myc/1'>c-Myc</scene> is a protein that binds to DNA and regulates transcription, a transcription factor. Bishop and collegues discovered viruses that induced chicken sarcomas. They studied the virus and identified an oncogene that would cause uncontrolled cellular proliferation. The viral oncogene that caused the sarcomas was identified as v-myc. Later on the homologous gene in chickens was discovered, and called c-myc. These findings provided evidence that activated c-Myc proteins were significant in cellular growth regulation.

==Role in Cancer==
[[Image:800px-Signal transduction v1.png|Apoptosis signal pathway|400 px|thumb]]
c-Myc is further along in the signal transduction pathway of the epithelial growth factor receptor (EGF receptor) which deals with the proliferation of cells. Mutations of c-Myc have a strong correlation to cancer. Normally c-myc is tightly regulated and c-Myc is short lived, but cancer cells express c-myc uncontrollably and are unable to degrade the c-Myc protein. This over expression and inability to rid the protein causes it to be active much longer. thus causing the over expression of genes needed for cell proliferation causing cancer. Over expression of c-Myc is prevalent in 80% of brest cancers, 70% colorectal cancers, 90% of gynecological cancers, 50% of hepatocellular carcinomas and is particularly prevalent Burkitt’s Lymphoma.

==Research of Structure and Function==
[[Image:C-Myc-DNA complex.png|c-Myc Dna complex|400 px|thumb]]
There are two main structures of the c-Myc proteins that are significant in its function. These are the Thr58 sight and the helix-loop-helix (HLH) motif surrounded by a basic amino acid region and a leucine zipper motif.

Kandil and colleagues speculated that the carboxyl terminus of the c-Myc protein had a similar structure to that of the helix-loop-helix family of DNA-binding proteins. Their research showed that the <scene name='Kwon_sandbox/Hlh/1'>Helix-Loop-Helix Structure</scene> was in fact the <scene name='Kwon_sandbox/Dna_binding_domain/1'>DNA binding Domain</scene> of c-Myc and were able to establish the corresponding binding sequence as GACCACGTGGTC. This sequence was found to be present in regulatory regions of genes during replication. They compared DNA binding of c-Myc to HLH protein TFEB. They found that the two proteins had the same inner nucleotides, providing significant evidence of the homology. Kandil and colleagues then placed spacing between half-sites of the DNA binding site. The inability of c-Myc to bind to the altered site provided evidence that c-Myc dimerizes when bound to DNA.

Bahram and colleagues found that the mutation of <scene name='Kwon_sandbox/T58/1'>Thr58</scene> in c-Myc was prevalent in many cancers. They then researched the effect of Thr58 mutation and found that it was the ubiquitination site of the protein. Their in vitro experiment showed that c-Myc with Thr58 mutation had a longer turnover rate than wild type c-Myc. They also found that histadine-tagged ubiquitin octamers were unable to bind to Thr58 mutant c-Myc proteins but successfully did bind to wild type. This provided strong evidence that the site is indeed the ubiquitination site.

== References ==

----
Dang, C.V.(1999) c-Myc Target Genes Involved in Cell Growth, Apoptosis, and Metabolism. [http://www.ncbi.nlm.nih.gov/pubmed/9858526 Molecular and Cellular Biology], 19: 1-11.

Kandil, A.N. (1991) Determination of the c-MYC DNA-binding site. Proc. natl. Acad. Sci. USA Vol. 88, pp6162-6166, July 1991 Genetics

Bahram et al., 2000; c-Myc hot spot mutations in lymphomas result in inefficient ubiquitination and decreased proteasome-mediated turnover

Kwon sandbox

2009-11-03T15:57:07Z

Jason Kwon:

<applet load='2A93-custom.pdb' size='400' frame='true' align='right' caption='c-Myc is a [http://en.wikipedia.org/wiki/DNA-binding_protein DNA binding protein]' scene='C-Myc/Custom/2'/>

== Introduction ==

----

<scene name='Kwon_sandbox/C-myc/1'>c-Myc</scene> is a protein that binds to DNA and regulates transcription, a transcription factor. Bishop and collegues discovered viruses that induced chicken sarcomas. They studied the virus and identified an oncogene that would cause uncontrolled cellular proliferation. The viral oncogene that caused the sarcomas was identified as v-myc. Later on the homologous gene in chickens was discovered, and called c-myc. These findings provided evidence that activated c-Myc proteins were significant in cellular growth regulation.

==Role in Cancer==
[[Image:800px-Signal transduction v1.png|Apoptosis signal pathway|400 px|thumb]]
c-Myc is further along in the signal transduction pathway of the epithelial growth factor receptor (EGF receptor) which deals with the proliferation of cells. Mutations of c-Myc have a strong correlation to cancer. Normally c-myc is tightly regulated and c-Myc is short lived, but cancer cells express c-myc uncontrollably and are unable to degrade the c-Myc protein. This over expression and inability to rid the protein causes it to be active much longer. thus causing the over expression of genes needed for cell proliferation causing cancer. Over expression of c-Myc is prevalent in 80% of brest cancers, 70% colorectal cancers, 90% of gynecological cancers, 50% of hepatocellular carcinomas and is particularly prevalent Burkitt’s Lymphoma.

==Research of Structure and Function==
[[Image:C-Myc-DNA complex.png|c-Myc Dna complex|400 px|thumb]]
There are two main structures of the c-Myc proteins that are significant in its function. These are the Thr58 sight and the helix-loop-helix (HLH) motif surrounded by a basic amino acid region and a leucine zipper motif.

Kandil and colleagues speculated that the carboxyl terminus of the c-Myc protein had a similar structure to that of the helix-loop-helix family of DNA-binding proteins. Their research showed that the helix-loop-helix structure was in fact the <scene name='Kwon_sandbox/Dna_binding_domain/1'>DNA binding Domain</scene> of c-Myc and were able to establish the corresponding binding sequence as GACCACGTGGTC. This sequence was found to be present in regulatory regions of genes during replication. They compared DNA binding of c-Myc to HLH protein TFEB. They found that the two proteins had the same inner nucleotides, providing significant evidence of the homology. Kandil and colleagues then placed spacing between half-sites of the DNA binding site. The inability of c-Myc to bind to the altered site provided evidence that c-Myc dimerizes when bound to DNA.

Bahram and colleagues found that the mutation of <scene name='Kwon_sandbox/T58/1'>Thr58</scene> in c-Myc was prevalent in many cancers. They then researched the effect of Thr58 mutation and found that it was the ubiquitination site of the protein. Their in vitro experiment showed that c-Myc with Thr58 mutation had a longer turnover rate than wild type c-Myc. They also found that histadine-tagged ubiquitin octamers were unable to bind to Thr58 mutant c-Myc proteins but successfully did bind to wild type. This provided strong evidence that the site is indeed the ubiquitination site.

== References ==

----
Dang, C.V.(1999) c-Myc Target Genes Involved in Cell Growth, Apoptosis, and Metabolism. [http://www.ncbi.nlm.nih.gov/pubmed/9858526 Molecular and Cellular Biology], 19: 1-11.

Kandil, A.N. (1991) Determination of the c-MYC DNA-binding site. Proc. natl. Acad. Sci. USA Vol. 88, pp6162-6166, July 1991 Genetics

Bahram et al., 2000; c-Myc hot spot mutations in lymphomas result in inefficient ubiquitination and decreased proteasome-mediated turnover

Kwon sandbox

2009-11-03T15:34:27Z

Jason Kwon:

<applet load='2A93-custom.pdb' size='400' frame='true' align='right' caption='c-Myc is a [http://en.wikipedia.org/wiki/DNA-binding_protein DNA binding protein]' scene='C-Myc/Custom/2'/>

== Introduction ==

----

<scene name='Kwon_sandbox/C-myc/1'>c-Myc</scene> is a protein that binds to DNA and regulates transcription, a transcription factor. Bishop and collegues discovered viruses that induced chicken sarcomas. They studied the virus and identified an oncogene that would cause uncontrolled cellular proliferation. The viral oncogene that caused the sarcomas was identified as v-myc. Later on the homologous gene in chickens was discovered, and called c-myc. These findings provided evidence that activated c-Myc proteins were significant in cellular growth regulation.

==Role in Cancer==
[[Image:800px-Signal transduction v1.png|Apoptosis signal pathway|400 px|thumb]]
c-Myc is further along in the signal transduction pathway of the epithelial growth factor receptor (EGF receptor) which deals with the proliferation of cells. Mutations of c-Myc have a strong correlation to cancer. Normally c-myc is tightly regulated and c-Myc is short lived, but cancer cells express c-myc uncontrollably and are unable to degrade the c-Myc protein. This over expression and inability to rid the protein causes it to be active much longer. thus causing the over expression of genes needed for cell proliferation causing cancer. Over expression of c-Myc is prevalent in 80% of brest cancers, 70% colorectal cancers, 90% of gynecological cancers, 50% of hepatocellular carcinomas and is particularly prevalent Burkitt’s Lymphoma.

==Research of Structure and Function==
[[Image:C-Myc-DNA complex.png|c-Myc Dna complex|400 px|thumb]]
There are two main structures of the c-Myc proteins that are significant in its function. These are the Thr58 sight and the helix-loop-helix (HLH) motif surrounded by a basic amino acid region and a leucine zipper motif.

Kandil and colleagues speculated that the carboxyl terminus of the c-Myc protein had a similar structure to that of the helix-loop-helix family of DNA-binding proteins. Their research showed that the helix-loop-helix structure was in fact the <scene name='Kwon_sandbox/Dna_binding_domain/1'>DNA binding Domain</scene> of c-Myc and were able to establish the corresponding binding sequence as GACCACGTGGTC. This sequence was found to be present in regulatory regions of genes during replication. They compared DNA binding of c-Myc to HLH protein TFEB. They found that the two proteins had the same inner nucleotides, providing significant evidence of the homology. Kandil and colleagues then placed spacing between half-sites of the DNA binding site. The inability of c-Myc to bind to the altered site provided evidence that c-Myc dimerizes when bound to DNA.

Bahram and colleagues found that the mutation of Thr58 in c-Myc was prevalent in many cancers. They then researched the effect of Thr58 mutation and found that it was the ubiquitination site of the protein. Their in vitro experiment showed that c-Myc with Thr58 mutation had a longer turnover rate than wild type c-Myc. They also found that histadine-tagged ubiquitin octamers were unable to bind to Thr58 mutant c-Myc proteins but successfully did bind to wild type. This provided strong evidence that the site is indeed the ubiquitination site.

== References ==

----
Dang, C.V.(1999) c-Myc Target Genes Involved in Cell Growth, Apoptosis, and Metabolism. [http://www.ncbi.nlm.nih.gov/pubmed/9858526 Molecular and Cellular Biology], 19: 1-11.

Kandil, A.N. (1991) Determination of the c-MYC DNA-binding site. Proc. natl. Acad. Sci. USA Vol. 88, pp6162-6166, July 1991 Genetics

Bahram et al., 2000; c-Myc hot spot mutations in lymphomas result in inefficient ubiquitination and decreased proteasome-mediated turnover

2009-11-03T01:09:41Z

Jason Kwon:

Template:GNF Protein box

2009-11-03T01:08:52Z

Jason Kwon: New page: {{GNF_Protein_box | image = C-Myc-DNA complex.png | image_source = Structure of the c-Myc (red) in complex with Max (blue) and DNA (PDB 1nkp). Both proteins are bin...

{{GNF_Protein_box
| image = C-Myc-DNA complex.png
| image_source = Structure of the c-Myc (red) in complex with Max (blue) and DNA ([[Protein_Data_Bank|PDB]] 1nkp). Both proteins are binding the major groove of the DNA by forming a fork-like structure.

| PDB = {{PDB2|1nkp}}
| Name = V-myc myelocytomatosis viral oncogene homolog (avian)
| HGNCid = 7553
| Symbol = MYC
| AltSymbols =; c-Myc
| OMIM = 190080
| ECnumber =
| Homologene = 31092
| MGIid = 97250
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005819 |text = spindle}}
| Process = {{GNF_GO|id=GO:0001836 |text = release of cytochrome c from mitochondria}} {{GNF_GO|id=GO:0006309 |text = DNA fragmentation during apoptosis}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0006357 |text = regulation of transcription from RNA polymerase II promoter}} {{GNF_GO|id=GO:0006879 |text = cellular iron ion homeostasis}} {{GNF_GO|id=GO:0006919 |text = caspase activation}} {{GNF_GO|id=GO:0007050 |text = cell cycle arrest}} {{GNF_GO|id=GO:0008284 |text = positive regulation of cell proliferation}} {{GNF_GO|id=GO:0008629 |text = induction of apoptosis by intracellular signals}} {{GNF_GO|id=GO:0008633 |text = activation of pro-apoptotic gene products}} {{GNF_GO|id=GO:0008634 |text = negative regulation of survival gene product activity}} {{GNF_GO|id=GO:0009314 |text = response to radiation}} {{GNF_GO|id=GO:0042981 |text = regulation of apoptosis}}
| Hs_EntrezGene = 4609
| Hs_Ensembl = ENSG00000136997
| Hs_RefseqProtein = NP_002458
| Hs_RefseqmRNA = NM_002467
| Hs_GenLoc_db = hg18
| Hs_GenLoc_chr =
| Hs_GenLoc_start =
| Hs_GenLoc_end =
| Hs_Uniprot =
| Mm_EntrezGene = 17869
| Mm_Ensembl = ENSMUSG00000022346
| Mm_RefseqmRNA = NM_010849
| Mm_RefseqProtein = NP_034979
| Mm_GenLoc_db = mm8
| Mm_GenLoc_chr = 15
| Mm_GenLoc_start = 61815052
| Mm_GenLoc_end = 61820027
| Mm_Uniprot = O88594
}}

Kwon sandbox

2009-11-03T01:08:32Z

Jason Kwon:

{{PBB|geneid=4609}}

'''Myc''' (cMyc) codes for a protein that binds to the DNA of other genes. When Myc is mutated, or overexpressed, the protein doesn't bind correctly, and often causes [[cancer]].

When a gene like Myc is altered to cause cancer, the cancerous version of the gene is called an [[oncogene]]. The healthy version of the gene that it is derived from is called a [[proto-oncogene]].

Myc gene encodes for a [[transcription factor]] that is believed to regulate expression of 15% of all genes <ref>Gearhart J, Pashos EE, Prasad MK, Pluripotency Redeux -- advances in stem-cell research, N Engl J Med 357(15):1469 [http://content.nejm.org/cgi/content/full/357/15/1469 Free full text]</ref> through binding on Enhancer Box sequences (E-boxes) and recruiting [[histone acetyltransferase]]s (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.

A mutated version of Myc is found in many cancers which causes Myc to be persistently expressed. This leads to the unregulated expression of many genes some of which are involved in cell proliferation and results in the formation of [[cancer]]. A common [[translocation]] which involves Myc is t(8:14) is involved in the development of a lymphoma. A recent study demontrated that temporary inhibition of Myc selectively kills mouse lung cancer cells, making it a potential cancer drug target.<ref>{{cite journal
| last = Soucek
| first = Laura
| authorlink =
| coauthors = Jonathan Whitfield, Carla P. Martins, Andrew J. Finch, Daniel J. Murphy, Nicole M. Sodir, Anthony N. Karnezis, Lamorna Brown Swigart, Sergio Nasi & Gerard I. Evan
| title = Modelling Myc inhibition as a cancer therapy
| journal = Nature
| volume = 455
| issue =
| pages = 679–683
| publisher = Nature Publishing Group
| location = London, UK
| date = [[2008-10-02]]
| url = http://www.nature.com/nature/journal/v455/n7213/abs/nature07260.html
| doi = 10.1038/nature07260
| id =
| accessdate = 2008-10-14}}</ref>

{{GNF_Protein_box
| image = C-Myc-DNA complex.png
| image_source = Structure of the c-Myc (red) in complex with Max (blue) and DNA ([[Protein_Data_Bank|PDB]] 1nkp). Both proteins are binding the major groove of the DNA by forming a fork-like structure.

| PDB = {{PDB2|1nkp}}
| Name = V-myc myelocytomatosis viral oncogene homolog (avian)
| HGNCid = 7553
| Symbol = MYC
| AltSymbols =; c-Myc
| OMIM = 190080
| ECnumber =
| Homologene = 31092
| MGIid = 97250
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005819 |text = spindle}}
| Process = {{GNF_GO|id=GO:0001836 |text = release of cytochrome c from mitochondria}} {{GNF_GO|id=GO:0006309 |text = DNA fragmentation during apoptosis}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0006357 |text = regulation of transcription from RNA polymerase II promoter}} {{GNF_GO|id=GO:0006879 |text = cellular iron ion homeostasis}} {{GNF_GO|id=GO:0006919 |text = caspase activation}} {{GNF_GO|id=GO:0007050 |text = cell cycle arrest}} {{GNF_GO|id=GO:0008284 |text = positive regulation of cell proliferation}} {{GNF_GO|id=GO:0008629 |text = induction of apoptosis by intracellular signals}} {{GNF_GO|id=GO:0008633 |text = activation of pro-apoptotic gene products}} {{GNF_GO|id=GO:0008634 |text = negative regulation of survival gene product activity}} {{GNF_GO|id=GO:0009314 |text = response to radiation}} {{GNF_GO|id=GO:0042981 |text = regulation of apoptosis}}
| Hs_EntrezGene = 4609
| Hs_Ensembl = ENSG00000136997
| Hs_RefseqProtein = NP_002458
| Hs_RefseqmRNA = NM_002467
| Hs_GenLoc_db = hg18
| Hs_GenLoc_chr =
| Hs_GenLoc_start =
| Hs_GenLoc_end =
| Hs_Uniprot =
| Mm_EntrezGene = 17869
| Mm_Ensembl = ENSMUSG00000022346
| Mm_RefseqmRNA = NM_010849
| Mm_RefseqProtein = NP_034979
| Mm_GenLoc_db = mm8
| Mm_GenLoc_chr = 15
| Mm_GenLoc_start = 61815052
| Mm_GenLoc_end = 61820027
| Mm_Uniprot = O88594
}}

<scene name='C-Myc/Custom/2'>TextToBeDisplayed</scene>

==Discovery==

Myc gene was first discovered in [[Burkitt's lymphoma]] patients. In Burkitt's lymphoma, cancer cells show [[chromosomal translocation]]s, 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 protein 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.

Myc [[mRNA]] contains an [[IRES]] (internal ribosome entry site) that allows the RNA to be translated into protein when [[5' cap]] dependent translation is inhibited; such as during viral infection.

==Molecular Function==

Myc protein is a [[transcription factor]] that activates expression of a great number of genes through binding on [[consensus sequence]]s (Enhancer Box sequences (E-boxes)) and recruiting [[histone acetyltransferase]]s (HATs). It can also act as a transcriptional repressor. By binding Miz-1 transcription factor and displacing the [[EP300|p300]] [[co-activator]], it inhibits expression of Miz-1 target genes.

Myc is activated upon various [[mitogen|mitogenic signal]]s such as [[Wnt signalling pathway|Wnt]], [[Sonic hedgehog|Shh]] and [[Epidermal growth factor|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]] (downregulates [[Bcl-2]]), differentiation and [[stem cell]] self-renewal. Myc is a very strong [[Oncogene#Proto-oncogene|proto-oncogene]] and it is very often found to be [[upregulation|upregulated]] in many types of cancers.

Kwon sandbox

2009-11-03T01:07:56Z

Jason Kwon:

Kwon sandbox

2009-11-03T01:06:35Z

Jason Kwon:

Kwon sandbox

2009-09-17T13:11:45Z

Jason Kwon: /* Introduction */

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{{STRUCTURE_3cin | PDB=3cin | SCENE= }}

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<scene name='C-Myc/Custom/2'>TextToBeDisplayed</scene>

== Introduction ==

----

<scene name='C-Myc/Custom/2'>TextToBeDisplayed</scene>

The c-Myc is a protonocogene, has the potential of becoming an oncogene if it under went specific mutations. This protein has been found to be mutated in Burkitt's lymphoma cell lines. The c-Myc protein is a transcription factor that regulates the expression of cell proliferation proteins. This protein is normally short lived, but when it has a point mutation that causes Thr58, it has been shown to have a much longer turnover rate.

Kwon sandbox

2009-09-17T13:10:34Z

Jason Kwon: New page: ==This is a placeholder== This is a placeholder text to help you get started in placing a Jmol applet on your page. At any time, click "Show Preview" at the bottom of this page to see how...

==This is a placeholder==
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placing a Jmol applet on your page. At any time, click
"Show Preview" at the bottom of this page to see how it goes.

Replace the PDB id (use lowercase!) after the STRUCTURE_ and after PDB= to load
and display another structure.

{{STRUCTURE_3cin | PDB=3cin | SCENE= }}

==This is a placeholder==
This is a placeholder text to help you get started in
placing a Jmol applet on your page. At any time, click
"Show Preview" at the bottom of this page to see how it goes.

Replace the PDB id (use lowercase!) after the STRUCTURE_ and after PDB= to load
and display another structure.

== Introduction ==

----

<scene name='C-Myc/Custom/2'>TextToBeDisplayed</scene>

The c-Myc is a protonocogene, has the potential of becoming an oncogene if it under went specific mutations. This protein has been found to be mutated in Burkitt's lymphoma cell lines. The c-Myc protein is a transcription factor that regulates the expression of cell proliferation proteins. This protein is normally short lived, but when it has a point mutation that causes Thr58, it has been shown to have a much longer turnover rate.