[Multifunctionality of MDM2 protein and its role in genomic instability of cancer cells].
Numerous studies have revealed that MDM2 oncoprotein is upregulated in different types of cancer. Additionally, it was demonstrated that in some cases, MDM2 may inhibit the neoplastic transformation process. In other words, MDM2 protein can be considered as an oncogene or as a tumor suppressor depending on the appropriate cellular context. MDM2 functions on different levels in the cell, which is a consequence of its complex structure, a plethora of interacting partners and regulation through numerous postranslational modifications. Thus, an alteration of the delicate balance in MDM2 activity can influence transformation and cancer development. Genomic instability is a hallmark of cancer, which inversely correlates to the activity of DNA damage response. In the case of not transformed cells MDM2 inhibits double strand brakes (DSBs) repair, hence stimulating carcinogenesis. In cancer cells MDM2 stimulates cytostatic-induced DSBs repair, thus leading to chemoresistance.
Marta
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Małuszek
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2