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@article{1310481,
author = {Adámik, Matej and Bažantová, Pavla and Navrátilová, Lucie and Polášková, Alena and Pečinka, Petr and Holaňová, Lucie and Tichý, Vlastimil and Brázdová, Marie},
article_location = {SAN DIEGO},
article_number = {1},
doi = {http://dx.doi.org/10.1016/j.bbrc.2014.11.027},
keywords = {p53 protein family; Sequence-specific DNA binding; Heavy metals; Cadmium; Cobalt; Nickel},
language = {eng},
issn = {0006-291X},
journal = {Biochemical and biophysical research communications},
title = {Impact of cadmium, cobalt and nickel on sequence-specific DNA binding of p63 and p73 in vitro and in cells},
url = {http://dx.doi.org/10.1016/j.bbrc.2014.11.027},
volume = {456},
year = {2015}
}
TY - JOUR
ID - 1310481
AU - Adámik, Matej - Bažantová, Pavla - Navrátilová, Lucie - Polášková, Alena - Pečinka, Petr - Holaňová, Lucie - Tichý, Vlastimil - Brázdová, Marie
PY - 2015
TI - Impact of cadmium, cobalt and nickel on sequence-specific DNA binding of p63 and p73 in vitro and in cells
JF - Biochemical and biophysical research communications
VL - 456
IS - 1
SP - 29-34
EP - 29-34
PB - ACADEMIC PRESS INC ELSEVIER SCIENCE
SN - 0006291X
KW - p53 protein family
KW - Sequence-specific DNA binding
KW - Heavy metals
KW - Cadmium
KW - Cobalt
KW - Nickel
UR - http://dx.doi.org/10.1016/j.bbrc.2014.11.027
L2 - http://dx.doi.org/10.1016/j.bbrc.2014.11.027
N2 - Site-specific DNA recognition and binding activity belong to common attributes of all three members of tumor suppressor p53 family proteins: p53, p63 and p73. It was previously shown that heavy metals can affect p53 conformation, sequence-specific binding and suppress p53 response to DNA damage. Here we report for the first time that cadmium, nickel and cobalt, which have already been shown to disturb various DNA repair mechanisms, can also influence p63 and p73 sequence-specific DNA binding activity and transactivation of p53 family target genes. Based on results of electrophoretic mobility shift assay and luciferase reporter assay, we conclude that cadmium inhibits sequence-specific binding of all three core domains to p53 consensus sequences and abolishes transactivation of several promoters (e.g. BAX and MDM2) by 50 mu M concentrations. In the presence of specific DNA, all p53 family core domains were partially protected against loss of DNA binding activity due to cadmium treatment. Effective cadmium concentration to abolish DNA-protein interactions was about two times higher for p63 and p73 proteins than for p53. Furthermore, we detected partial reversibility of cadmium inhibition for all p53 family members by EDTA. DTT was able to reverse cadmium inhibition only for p53 and p73. Nickel and cobalt abolished DNA-p53 interaction at sub-millimolar concentrations while inhibition of p63 and p73 DNA binding was observed at millimolar concentrations. In summary, cadmium strongly inhibits p53, p63 and p73 DNA binding in vitro and in cells in comparison to nickel and cobalt. The role of cadmium inhibition of p53 tumor suppressor family in carcinogenesis is discussed. (C) 2014 Elsevier Inc. All rights reserved.
ER -
ADÁMIK, Matej, Pavla BAŽANTOVÁ, Lucie NAVRÁTILOVÁ, Alena POLÁŠKOVÁ, Petr PEČINKA, Lucie HOLAŇOVÁ, Vlastimil TICHÝ a Marie BRÁZDOVÁ. Impact of cadmium, cobalt and nickel on sequence-specific DNA binding of p63 and p73 in vitro and in cells. \textit{Biochemical and biophysical research communications}. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE, 2015, roč.~456, č.~1, s.~29-34. ISSN~0006-291X. Dostupné z: https://dx.doi.org/10.1016/j.bbrc.2014.11.027.
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