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Pregled bibliografske jedinice broj: 1052925

Functional interplay between p53 and p53/p73, NME and GLI protein families in human melanoma


Ozretić, Petar; Radić, Martina; Hanžić, Nikolina; Proust, Bastien; Sabol, Maja; Trnski, Diana; Musani, Vesna; Jazvinšćak Jembrek, Maja; Ciribilli, Yari; Milas, Ivan et al.
Functional interplay between p53 and p53/p73, NME and GLI protein families in human melanoma // HDBMB2019 Crossroads in Life Sciences / Katalinić, Maja ; Dulić, Morana ; Stuparević, Igor (ur.).
Zagreb: Croatian Society of Biochemistry and Molecular Biology, 2019. str. 43-43 (pozvano predavanje, nije recenziran, sažetak, znanstveni)


CROSBI ID: 1052925 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Functional interplay between p53 and p53/p73, NME and GLI protein families in human melanoma

Autori
Ozretić, Petar ; Radić, Martina ; Hanžić, Nikolina ; Proust, Bastien ; Sabol, Maja ; Trnski, Diana ; Musani, Vesna ; Jazvinšćak Jembrek, Maja ; Ciribilli, Yari ; Milas, Ivan ; Puljiz, Zvonimir ; Bosnar Herak, Maja ; Levanat, Sonja ; Slade, Neda

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

Izvornik
HDBMB2019 Crossroads in Life Sciences / Katalinić, Maja ; Dulić, Morana ; Stuparević, Igor - Zagreb : Croatian Society of Biochemistry and Molecular Biology, 2019, 43-43

ISBN
978-953-95551-7-5

Skup
Congress of the Croatian Society of Biochemistry and Molecular Biology HDBMB2019 "Crossroads in Life Sciences"

Mjesto i datum
Lovran, Hrvatska, 25-28.09.2019

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
melanoma ; p53 ; p73 ; NME ; GLI

Sažetak
Unlike other tumors, TP53 is rarely mutated in melanoma ; however, it fails to function as a tumor suppressor. We assume that its functions might be altered through interactions with several families of proteins, including p53/p73, NME and GLI. To elucidate the potential interplay among these families we analysed the expression profiles of aforementioned genes and proteins in a panel of melanoma cell lines, metastatic melanoma specimens and healthy corresponding tissue. Using qPCR, a higher level of NME1 gene expression and lower levels of Δ40p53β, ΔNp73, GLI1, GLI2 and PTCH1 were observed in tumor samples compared to healthy tissue. Protein expression of Δ133p53α, Δ160p53α and ΔNp73α isoforms, NME1 and NME2, and N’ΔGLI1, GLI1FL, GLI2ΔN isoforms was elevated in tumor tissue, whereas ∆Np73β was downregulated. The results in melanoma cell lines, in general, support these findings. In addition, we correlated expression profiles with clinical features and outcome. Higher Δ133p53β and p53α mRNA and both GLI1 mRNA and GLI3R protein expression had a negative impact on the overall survival. Shorter overall survival was also connected with lower p53β and NME1 gene expression levels. Furthermore, we examined the interactions between p53 and the proteins of interest as well as the effect of p53/p73 isoforms, NME and GLI on p53 transactivation capacity in wild- type p53 melanoma cell lines. As expected, we have found interactions between p53α and small molecular weight p53 isoforms (p53β, p53γ, Δ40p53α, Δ40p53β and Δ133p53α) well as with both ΔNp73α and ΔNp73β in melanoma cell lines. These results suggest that p53 and p73 isoforms may contribute to inactivation of p53 protein function in melanoma cells by forming the direct protein interactions. Consequently, reporter and apoptosis assay confirmed that p53 and p73 isoforms interfere with p53α activity thus regulating the expression of genes involved in cell cycle, apoptosis and senescence. Although NME and GLI did not form direct complexes with p53, they were able to modify its activity. In conclusion, all examined genes may have implications in melanoma development and functional inactivity of TP53. Targeting two independent pathways could be a promising strategy in melanoma treatment.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekti:
HRZZ-IP-2013-11-1615 - Otkrivanje novih proteinskih interakcija kao podloga za nove pristupe liječenju melanoma čovjeka (ProNetMel) (Slade, Neda, HRZZ - 2013-11) ( POIROT)

Ustanove:
Institut "Ruđer Bošković", Zagreb,
KBC "Sestre Milosrdnice"


Citiraj ovu publikaciju

Ozretić, Petar; Radić, Martina; Hanžić, Nikolina; Proust, Bastien; Sabol, Maja; Trnski, Diana; Musani, Vesna; Jazvinšćak Jembrek, Maja; Ciribilli, Yari; Milas, Ivan et al.
Functional interplay between p53 and p53/p73, NME and GLI protein families in human melanoma // HDBMB2019 Crossroads in Life Sciences / Katalinić, Maja ; Dulić, Morana ; Stuparević, Igor (ur.).
Zagreb: Croatian Society of Biochemistry and Molecular Biology, 2019. str. 43-43 (pozvano predavanje, nije recenziran, sažetak, znanstveni)
Ozretić, P., Radić, M., Hanžić, N., Proust, B., Sabol, M., Trnski, D., Musani, V., Jazvinšćak Jembrek, M., Ciribilli, Y. & Milas, I. (2019) Functional interplay between p53 and p53/p73, NME and GLI protein families in human melanoma. U: Katalinić, M., Dulić, M. & Stuparević, I. (ur.)HDBMB2019 Crossroads in Life Sciences.
@article{article, year = {2019}, pages = {43-43}, keywords = {melanoma, p53, p73, NME, GLI}, isbn = {978-953-95551-7-5}, title = {Functional interplay between p53 and p53/p73, NME and GLI protein families in human melanoma}, keyword = {melanoma, p53, p73, NME, GLI}, publisher = {Croatian Society of Biochemistry and Molecular Biology}, publisherplace = {Lovran, Hrvatska} }
@article{article, year = {2019}, pages = {43-43}, keywords = {melanoma, p53, p73, NME, GLI}, isbn = {978-953-95551-7-5}, title = {Functional interplay between p53 and p53/p73, NME and GLI protein families in human melanoma}, keyword = {melanoma, p53, p73, NME, GLI}, publisher = {Croatian Society of Biochemistry and Molecular Biology}, publisherplace = {Lovran, Hrvatska} }




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