TY - JOUR
TI - Sp1 binds to the external promoter of the p73 gene and induces the
expression of TAp73 gamma in lung cancer
AU - Logotheti, Stella
AU - Michalopoulos, Ioannis
AU - Sideridou, Maria and
AU - Daskalos, Alexandros
AU - Kossida, Sophia
AU - Spandidos, Demetrios A. and
AU - Field, John K.
AU - Vojtesek, Borek
AU - Liloglou, Triantafyllos and
AU - Gorgoulis, Vassilis
AU - Zoumpourlis, Vassilis
JO - FEBS Journal
PY - 2010
VL - 277
TODO - 14
SP - 3014-3027
PB - Wiley
SN - 1742-464X, 1742-4658
TODO - 10.1111/j.1742-4658.2010.07710.x
TODO - lung cancer; P1 promoter; p73 isoforms; Sp1; TAp73 gamma; Delta Np73
TODO - The p73 gene possesses an extrinsic P1 promoter and an intrinsic P2
promoter, resulting in TAp73 and Delta Nu p73 isoforms, respectively.
The ultimate effect of p73 in oncogenesis is thought to depend on the
apoptotic TA to antiapoptotic Delta N isoforms’ ratio. This study was
aimed at identifying novel transcription factors that affect TA isoform
synthesis. With the use of bioinformatics tools, in vitro binding
assays, and chromatin immunoprecipitation analysis, a region extending
-233 to -204 bp upstream of the transcription start site of the human
p73 P1 promoter, containing conserved Sp1-binding sites, was
characterized. Treatment of cells with Sp1 RNAi and Sp1 inhibitor
functionally suppress TAp73 expression, indicating positive regulation
of P1 by the Sp1 protein. Notably Sp1 inhibition or knockdown also
reduces Delta Nu p73 protein levels. Therefore, Sp1 directly regulates
TAp73 transcription and affects Delta Nu p73 levels in lung cancer.
TAp73 gamma was shown to be the only TA isoform overexpressed in several
lung cancer cell lines and in 26 non-small cell lung cancers, consistent
with Sp1 overexpression, thereby questioning the apoptotic role of this
specific p73 isoform in lung cancer.
ER -