Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions.
Apurinic/apyrimidinic endonuclease 1 (APE1), an essential protein in mammals, is involved in base excision DNA repair (BER) and in regulation of gene expression, acting as a redox co-activator of several transcription factors. Recent findings highlight a novel role for APE1 in RNA metabolism, which is modulated by nucleophosmin (NPM1). The results reported in this article show that five lysine residues (K24, K25, K27, K31 and K32), located in the APE1 N-terminal unstructured domain, are involved in the interaction of APE1 with both RNA and NPM1, thus supporting a competitive binding mechanism. Data from kinetic experiments demonstrate that the APE1 N-terminal domain also serves as a device for fine regulation of protein catalytic activity on abasic DNA. Interestingly, some of these critical lysine residues undergo acetylation in vivo. These results suggest that protein-protein interactions and/or post-translational modifications involving APE1 N-terminal domain may play important in vivo roles, in better coordinating and fine-tuning protein BER activity and function on RNA metabolism.
Fantini
Damiano
D
Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy.
Vascotto
Carlo
C
Marasco
Daniela
D
D'Ambrosio
Chiara
C
Romanello
Milena
M
Vitagliano
Luigi
L
Pedone
Carlo
C
Poletto
Mattia
M
Cesaratto
Laura
L
Quadrifoglio
Franco
F
Scaloni
Andrea
A
Radicella
J Pablo
JP
Tell
Gianluca
G
D000107:Acetylation; D000595:Amino Acid Sequence; D001665:Binding Sites; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008969:Molecular Sequence Data; D000090243:Nucleophosmin; D010455:Peptides / Q000378:metabolism; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D020539:Sequence Analysis, Protein
C000716967:NPM1 protein, human; D010455:Peptides; D000090243:Nucleophosmin; D012313:RNA; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D008239:Lysine