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L. Tuosto - CD28 co-stimulatory molecule as a key regulator of T lymphocyte differentiation and survival
nalling cascades relating CD28 stimulation to both
actin reorganization and NF-κB activation. Our preliminary
data indicate that CD28 is also involved in
the recruitment of a complex containing Vav-1 and
Nck. Nck is an adapter that plays a key role in the
remodelling of actin cytoskeleton following TCR
stimulation, through the specific interaction with the
CD3ε chain, thus favouring TCR/CD3 signalling
and T cell activation. In particular, we observed that
stimulation of T cells with B7 expressing APC
induces the association of CD28 with Nck and the
recruitment to CD28 of a complex containing Vav-
1, Nck and actin (Fig. 1).
Experiments are in progress to characterize the
nature of CD28/Nck/Vav interaction, in order to
identify the domains of CD28, Nck and Vav1
involved in their reciprocal association.
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Selected publications
Annibaldi A, Sajeva A, Muscolini M, Ciccosanti F,
Corazzari M, Piacentini M, Tuosto L. CD28 ligation
in the absence of TCR promotes RelA/NF-kappaB
recruitment and trans-activation of the HIV-1 LTR.
Eur J Immunol. 2008, 38:1446-51.
Cianfrocca R, Muscolini M, Marzano V, Annibaldi A,
Marinari B, Levrero M, Costanzo A, Tuosto L.
RelA/NF-kappaB recruitment on the bax gene promoter
antagonizes p73-dependent apoptosis in costimulated
T cells. Cell Death Differ. 2008, 15:354-63.
Muscolini M, Cianfrocca R, Sajeva A, Mozzetti S,
Ferrandina G, Costanzo A, Tuosto L. Trichostatin A
up-regulates p73 and induces Bax-dependent apoptosis
in cisplatin-resistant ovarian cancer cells. Mol
Cancer Ther. 2008, 7:1410-9.
Fig. 1 - Jurkat JCH7C17 cells expressing CD28 WT were transfected with 15µg of Vav-GFP and 15µg HA-NCK for 6 h, then activated with
5-3.1/B7 cells for 15 min and seeded on cover glasses. After fixing and permeabilization, Nck was stained with a rabbit anti-Nck antiserum
followed by Alexa fluor 594-conjugated goat anti-rabbit secondary antibody. Slides were analyzed by using a Zeiss LSM510 META confocal
microscope. Bar, 10 µm.