The carcinogenicity of nickel compounds has been confirmed and corroborated by numerous epidemiological studies in humans and carcinogenesis bioassays in animals [1]. Although the mechanisms of nickel-induced carcinogenesis are not well-known, they are believed to involve genetic and epigenetic routes. Nickel compounds influence carcinogenesis by interfering with a variety of cellular targets. We found that nickel is a potent inhibitor in vivo of histone H4 acetylation, in both yeast and mammalian cells [2]. It has preference to specific lysine residues in the N-terminal -S1GRGK5GGK8GLGK12GGAK16RH18RKVL22 histone H4, in which the sites of acetylation are clustered. The metal ion is able to bind histidine H18 in the N-terminal which protrude out from the nucleosome [3]. We also found that an excellent tumour marker recently discovered and specifically induced by nickel, Cap43 protein, has a new mono-histidinic motif consisting of ten amino acids TRSRSHTSEG repeated three times in the C-terminus which is able to bind several metal ions in a cooperative way [4,5].
Molecular Mechanisms of Nickel Carcinogenesis: Nickel Binding to Histone H4 and Cap43 Protein / Zoroddu, Maria Antonietta; Peana, Massimiliano Francesco; Medici, Serenella. - (2005), pp. 70-70. (Intervento presentato al convegno III° Conferenza nazionale, Inquinamento da metalli pesanti: la biodisponibilità tenutosi a Sassari. Italia nel 5-6 Maggio 2005).
Molecular Mechanisms of Nickel Carcinogenesis: Nickel Binding to Histone H4 and Cap43 Protein
ZORODDU, Maria Antonietta;PEANA, Massimiliano Francesco;MEDICI, Serenella
2005-01-01
Abstract
The carcinogenicity of nickel compounds has been confirmed and corroborated by numerous epidemiological studies in humans and carcinogenesis bioassays in animals [1]. Although the mechanisms of nickel-induced carcinogenesis are not well-known, they are believed to involve genetic and epigenetic routes. Nickel compounds influence carcinogenesis by interfering with a variety of cellular targets. We found that nickel is a potent inhibitor in vivo of histone H4 acetylation, in both yeast and mammalian cells [2]. It has preference to specific lysine residues in the N-terminal -S1GRGK5GGK8GLGK12GGAK16RH18RKVL22 histone H4, in which the sites of acetylation are clustered. The metal ion is able to bind histidine H18 in the N-terminal which protrude out from the nucleosome [3]. We also found that an excellent tumour marker recently discovered and specifically induced by nickel, Cap43 protein, has a new mono-histidinic motif consisting of ten amino acids TRSRSHTSEG repeated three times in the C-terminus which is able to bind several metal ions in a cooperative way [4,5].I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.