phylogenetic study of mdm2

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Phylogenetic Study of mdm2 Yosok PunY

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A phylogenetic study og Mdm2 using tools like ClustalW2 and unrooted trees.

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Page 1: Phylogenetic Study of Mdm2

Phylogenetic Study of mdm2Yosok PunY

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p53 and mdm2 interactions

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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

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Mdm2

Increased levels of mdm2 found in:

Soft tissue sarcomas Osteosarcomas Breast tumors

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Cn3D

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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

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JalView

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Mdm2 [Homo sapiens] FASTA

>gi|155183770|gb|ABT17086.1| Mdm2 [Homo sapiens]

MCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQYIMTKRLYDEK

QQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVNQQESSDSGTSVSENRCHLEGGSDQKDLVQ

ELQEEKPSSSHLVSRPSTSSRRRAISETEENSDELSGERQRKRHKSDSISLSFDESLALCVIREICCERS

SSSESTGTPSNPDLDAGVSEHSGDWLDQDSVSDQFSVEFEVESLDSE

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ClustalW2

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HomoloGene

Homologs were discovered in these vertebrates:

Chimpanzee, Rhesus macaque, Dog, Cattle, House mouse, Brown rat, Red Junglefowl, Zebrafish

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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.