XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
36.
THE ROLE OF NFI IN P21 GENE EXPRESSION
Miroslava Kretová, Ľudmila Šabová and Katarína Luciaková
Laboratory of Molecular Biology, Cancer Research Institute SAS Bratislava
p21 protein was originally identified as an inhibitor of cell cycle dependent kinases (CDK).
p21 plays an important role in cell cycle arrest at the G1/ S checkpoint in response to
DNA damage. p21 also modulates various processes such as cell growth, differentiation
and apoptosis. p21 gene expression is mainly regulated at transcription level. The key
regulator of p21 gene expression is tumor suppressor protein p53. However, expression
of p21 may be either p53-dependent or p53-independent, which results in a network of
control mechanisms influencing the cell cycle. Transcription factor NFI (nuclear factor-I) is
a repressor of p21 transription. NFI and Sp1-binding sites, which play an important role
in p21 gene expression, were identified in the p21 proximal promoter. The transforming
growth factor β (TGF-β) activates p21 gene in G1 phase of the cell cycle. Molecular
mechanism of the stress-induced expression of p21 is not well understood. TGF-β
may activate signaling pathways affecting the target gene expression either directly
by phosphorylation of Smad proteins or indirectly by activation of the MAPK signaling
pathway. The aim of our work is to identify the signaling pathway(s) playing a role in the
regulation of p21 gene in serum starved cells and in TGF-β-treated cells. Transfection of
recombinant constructs bearing mutations and deletion of NFI binding sites in the p21
promoter was used to measure the level of p21 expression in HaCaT, HCT-116 and JEG-3
cells during cellular stress.
Acknowledgements: This work was supported by VEGA grant No. 2/0074/08.
154 XXII. Biochemistry Congress, Martin