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Phylogenetic Study of mdm2
Yosok PunY
p53 and mdm2 interactions
Mdm2

Negative regulator of p53 tumor suppressor
gene

Discovery from transformed mouse cell line

Mdm2 over expression with Ras oncogene led
to tumor formation in nude mice

Human homolog is sometimes called Hdm2
Mdm2

Increased levels of
mdm2 found in:

Soft tissue sarcomas

Osteosarcomas

Breast tumors
Cn3D
E3 ligase activity

Targets both itself and p53
for degradation by
proteasome

Inhibitor of MDM2-p53
interactions is nutlin

MDM2 also interacts with
ubiquitin protease, USP7
that reverses
ubiquitylation to prevent
degradation with
proteasome

Fine regulatory circuit
JalView
Mdm2 [Homo sapiens] FASTA
>gi|155183770|gb|ABT17086.1| Mdm2 [Homo sapiens]
MCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQYIMTKRLYDEK
QQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVNQQESSDSGTSVSENRCHLEGGSDQKDLVQ
ELQEEKPSSSHLVSRPSTSSRRRAISETEENSDELSGERQRKRHKSDSISLSFDESLALCVIREICCERS
SSSESTGTPSNPDLDAGVSEHSGDWLDQDSVSDQFSVEFEVESLDSE
ClustalW2
HomoloGene
Homologs were
discovered in these
vertebrates:
Chimpanzee, Rhesus
macaque, Dog,
Cattle, House mouse,
Brown rat, Red
Junglefowl, Zebrafish
References

Harris. Curtis C. et. al. Proceedings of the National Academy of Sciences.
http://www.pnas.org/content/103/6/1659/F1.expansion.html. Accessed May
7th
2013.

Proteasome. Wikipedia. http://en.wikipedia.org/wiki/Proteasome. Accessed
May 7th
2013

Mdm2. Wikipedia. http://en.wikipedia.org/wiki/Mdm2. Accessed May 7th
2013.

Knappskog et. al. MDM2 promoter SNP285 and SNP309; phylogeny and
impact on cancer risk. PubMed Central.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260817/. Accessed May 13th
2013

Jayaraman A et. al. The interaction of p53 and MDM2 genes in cancers, in
silico studies and phylogenetic analysis. Biology and Medicine Vol 3 (3): 01-
12, 2011.

Databases/Tools Used: NCBI Protein. NCBI BLASTp. ClustalW2.
ClustalW2 Phylogeny. Cn3D. HomoloGene.

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Phylogenetic Study of Mdm2

  • 1. Phylogenetic Study of mdm2 Yosok PunY
  • 2. p53 and mdm2 interactions
  • 3. Mdm2  Negative regulator of p53 tumor suppressor gene  Discovery from transformed mouse cell line  Mdm2 over expression with Ras oncogene led to tumor formation in nude mice  Human homolog is sometimes called Hdm2
  • 4. Mdm2  Increased levels of mdm2 found in:  Soft tissue sarcomas  Osteosarcomas  Breast tumors
  • 5.
  • 6.
  • 7.
  • 9. E3 ligase activity  Targets both itself and p53 for degradation by proteasome  Inhibitor of MDM2-p53 interactions is nutlin  MDM2 also interacts with ubiquitin protease, USP7 that reverses ubiquitylation to prevent degradation with proteasome  Fine regulatory circuit
  • 11.
  • 12. Mdm2 [Homo sapiens] FASTA >gi|155183770|gb|ABT17086.1| Mdm2 [Homo sapiens] MCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQYIMTKRLYDEK QQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVNQQESSDSGTSVSENRCHLEGGSDQKDLVQ ELQEEKPSSSHLVSRPSTSSRRRAISETEENSDELSGERQRKRHKSDSISLSFDESLALCVIREICCERS SSSESTGTPSNPDLDAGVSEHSGDWLDQDSVSDQFSVEFEVESLDSE
  • 13.
  • 15.
  • 16.
  • 17. HomoloGene Homologs were discovered in these vertebrates: Chimpanzee, Rhesus macaque, Dog, Cattle, House mouse, Brown rat, Red Junglefowl, Zebrafish
  • 18. References  Harris. Curtis C. et. al. Proceedings of the National Academy of Sciences. http://www.pnas.org/content/103/6/1659/F1.expansion.html. Accessed May 7th 2013.  Proteasome. Wikipedia. http://en.wikipedia.org/wiki/Proteasome. Accessed May 7th 2013  Mdm2. Wikipedia. http://en.wikipedia.org/wiki/Mdm2. Accessed May 7th 2013.  Knappskog et. al. MDM2 promoter SNP285 and SNP309; phylogeny and impact on cancer risk. PubMed Central. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260817/. Accessed May 13th 2013  Jayaraman A et. al. The interaction of p53 and MDM2 genes in cancers, in silico studies and phylogenetic analysis. Biology and Medicine Vol 3 (3): 01- 12, 2011.  Databases/Tools Used: NCBI Protein. NCBI BLASTp. ClustalW2. ClustalW2 Phylogeny. Cn3D. HomoloGene.