Naslov
Modelling non canonical Notch interaction of dnMAML with p53 in breast cancer

Autori
Opačak-Bernardi, Teuta ; Brkić, Hrvoje ; Jukić, Marijana ; Glavaš-Obrovac, Ljubica

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
HDIR-5: “Translating Science to Medicine – Targets and Therapeutics” Fifth Meeting of the Croatian Association for Cancer Research with International Participation / Ozretić, Petar ; Levanat, Sonja - Zagreb, 2018, 66-66

Skup
HDIR-5: “Translating Science to Medicine – Targets and Therapeutics”

Mjesto i datum
Zagreb, Hrvatska, 08.11.2018. - 10.11.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Notch, breast cancer, p53

Sažetak
Notch signaling is one of the most important developmental pathways present in all organisms. Canonical branch of the signaling cascade affects target genes and regulates cell metabolism through regulation of expression. Non-canonical branch represents a complicated network of signaling crosstalk. The basis for non-canonical signaling is direct interaction with effectors from different signaling cascades, including but not limited to Akt, Hif, NFκB, mTOR and p53. This branch is still relatively undiscovered in spite of great impact it can have on cellular development. One of the possibilities of interaction is between p53 and MAML. The region of MAML responsible for interaction with p53 is located on the N-terminal portion of MAML, in the section that was identified as dnMAML due to its ability to inhibit canonical Notch. To test the hypothesis of dnMAMl affecting p53 availability in the cell dnMAML was incorporated into a carrier molecule to enable cellular delivery and tested on three breast cancer cells lines (MCF7, MDA-MB 231 and MDA-MB 468). The cells were chosen due to their difference in p53 status. Cells were treated with dnMAML and empty carrier to determine if there is a change in p53 quantity after treatment with dnMAML. p53 was identified using Western blot and its quantity in different samples determined by total protein evaluation. The treated samples showed decreased levels of p53 when dnMAMl was present compared to both untreated controls and samples treated with only the carrier protein. The interaction was then modeled in silico using structure information from the PDB database. The models were rendered using AutoDock software to find the best binding solution for the two molecules.The model can be used to further determine changes in binding profiles when different p53 mutations are taken into account. The presented results need to be further confirmed using direct interaction methods like mammalian two hybrid method, but show that there is still a great deal to be discovered about crosstalk between signaling cascades and even more about the role Notch pathway had in development and regulation of cellular fates in cancer.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Interdisciplinarne prirodne znanosti, Temeljne medicinske znanosti

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