Impact of cadmium, cobalt and nickel on sequence-specific DNA binding of p63 and p73 in vitro and in cells

0441591 - BFÚ 2015 RIV US eng J - Článek v odborném periodiku
Adámik, Matěj - Bažantová, Pavla - Navrátilová, Lucie - Polášková, Alena - Pečinka, Petr - Holanová, L. - Tichý, Vlastimil - Brázdová, Marie
Impact of cadmium, cobalt and nickel on sequence-specific DNA binding of p63 and p73 in vitro and in cells.
Biochemical and Biophysical Research Communications. Roč. 456, č. 1 (2015), s. 29-34. ISSN 0006-291X. E-ISSN 1090-2104
Grant CEP: GA ČR(CZ) GA13-36108S
Institucionální podpora: RVO:68081707
Klíčová slova: p53 protein family * Sequence-specific DNA binding * Heavy metals
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 2.371, rok: 2015

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.
Trvalý link: http://hdl.handle.net/11104/0244593