Mdm2

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Struttura tridimensionale della Mdm2

Mdm2 è il nome sia del gene che della corrispettiva proteina che svolge la funzione di principale inibitore di p53, andandosi a legare ad esso ed inducendone l'ubiquitinazione e quindi la degradazione tramite proteosoma. Mdm2 appartiene pertanto alla famiglia delle ligasi E3.[1][2]

Interazioni

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Mdm2 è regolata da molte proteine e miRNA per il suo ruolo centrale nel regolare p53. Interagisce con p53 inducendone la degradazione. Ciononostante p53 incrementa l'attività e la produzione di Mdm2 sia direttamente che indirettamente, formando così un feedback negativo autoregolatorio. La proteina ARF (conosciuta anche come p14) è un inibitore di Mdm2.

Mdm2 interagisce con le seguenti proteine:

Interazioni farmacologiche

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La molecola nutlina inibisce l'interazione tra Mdm2 e p53 incrementanto la stabilità di quest'ultimo, ciononostante è ancora in fase di sperimentazione.[50]

Note

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  1. ^ J. D. Oliner, K. W. Kinzler e P. S. Meltzer, Amplification of a gene encoding a p53-associated protein in human sarcomas, in Nature, vol. 358, n. 6381, 2 luglio 1992, pp. 80–83, DOI:10.1038/358080a0. URL consultato il 16 aprile 2018.
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  35. ^ Jin Y, Zeng SX, Dai MS, Yang XJ, Lu H, MDM2 inhibits PCAF (p300/CREB-binding protein-associated factor)-mediated p53 acetylation, in The Journal of Biological Chemistry, vol. 277, n. 34, August 2002, pp. 30838–43, DOI:10.1074/jbc.M204078200, PMID 12068014.
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