Citrullination at the N-terminal region of MDM2 by the PADI4 enzyme.

ABSTRACT: PADI4 is one of the human isoforms of a family of enzymes involved in the conversion of arginine to citrulline. MDM2 is an E3 ubiquitin ligase that is critical for degradation of the tumor suppressor gene p53. We have previously shown that there is an interaction between MDM2 and PADI4 in cellulo, and that such interaction occurs through the N-terminal region of MDM2, N-MDM2, and in particular through residues Thr26, Val28, Phe91, and Lys98. Here, by using a "divide-and-conquer" approach, we have designed and synthesized peptides comprising these two polypeptide stretches (residues Ala21-Lys36, and Lys94-Val108), either in the wild-type species or in their citrullinated versions. Some of the citrullinated peptides were aggregation-prone, as suggested by DOSY-NMR experiments, but the wild-t

SUBMITTER: Neira JL 

PROVIDER: S-EPMC11751894 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature