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Pregled bibliografske jedinice broj: 608686

Interaction of Gli1, SuFu and GSK3beta in centrosomes of HEK293 cells


Car, Diana; Sabol, Maja; Musani, Vesna; Ozretić, Petar; Levanat, Sonja
Interaction of Gli1, SuFu and GSK3beta in centrosomes of HEK293 cells // From molecules to life and back FEBS3+ Meeting Book of Abstracts / Dumić, Jerka ; Kovarik, Zrinka ; Varljen, Jadranka (ur.).
Rijeka: Croatian Society of Biochemistry and Moelcular Biology, 2012. str. 201-201 (poster, domaća recenzija, sažetak, znanstveni)


Naslov
Interaction of Gli1, SuFu and GSK3beta in centrosomes of HEK293 cells

Autori
Car, Diana ; Sabol, Maja ; Musani, Vesna ; Ozretić, Petar ; Levanat, Sonja

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

Izvornik
From molecules to life and back FEBS3+ Meeting Book of Abstracts / Dumić, Jerka ; Kovarik, Zrinka ; Varljen, Jadranka - Rijeka : Croatian Society of Biochemistry and Moelcular Biology, 2012, 201-201

ISBN
978-953-95551-4-4

Skup
From molecules to life and back FEBS3+ Meeting

Mjesto i datum
Opatija, Hrvatska, 13.-16.06.2012

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
Hedgehog signaling

Sažetak
The Hedgehog (Hh) signaling pathway is a developmental pathway, mostly inactivated in adult tissues. Aberrant activation has been found in various tumor types, such as lung, breast, ovarian and colon. The pathway is activated by the ligand Hedgehog that causes its receptor Patched to release its repression over the coreceptor Smoothened. This triggers a cascade of events in the cytoplasm leading to activation of transcription factor Gli1. The interactions between the transcription factor Gli1 and its regulators Suppressor of Fused (SuFu) and GSK3 or the role of GSK3 in activated cells are not fully understood yet. Recently the primary cilium was shown to play an important role in signal transduction. The human embryonic kidney cells, HEK293 show an interesting pattern of Gli1, SuFu and GSK3 accumulation in the centrosome, which gives rise to the basal body of the primary cilium. Since the primary cilia of these cells were undetectable we wanted to investigate if it is possible for these proteins to interact in the centrosome in the absence of a primary cilium. Exogenous Shh protein treatment causes a shift in protein localization, Gli1 translocates to the nucleus and SuFu remains in the cytoplasm. The amount of cells with visible accumulations of these proteins in the centrosome decreases from 80% to 19%. This suggests that the pathway is fully active and functioning properly. Preliminary results reveal that Gli1 and SuFu form a complex in these cells, suggesting that their interaction is independent of the primary cilium. Gli2 is undetectable in these cells, while Gli3 localizes to vesicles in the cytoplasm. Therefore it is likely that Gli1 is the main mediator of signal transduction. To examine the effect of GSK3inhibition on protein localization and interactions, we treated the cells with a GSK3 inhibitor (LiCl). Treatment elevates the pathway activity, increases expression of GLI1 and PTCH1 and also causes a shift in protein localization consistent with pathway activation. Our results propose that HEK293 cells have an active Hh signaling pathway, with the regulatory processes between Gli1, SuFu and GSK3 taking place in the centrosome.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
098-0982464-2461 - Prijenos signala u tumorima: Hh-Gli put, interakcije i potencijalne terapije (Sonja Levanat, )

Ustanove
Institut "Ruđer Bošković", Zagreb