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The ubiquitin–protein ligase activity of Hdm2 is inhibited by nucleic acids
Author(s) -
Linares Laëtitia K,
Scheffner Martin
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01108-6
Subject(s) - nucleic acid , dna ligase , ubiquitin ligase , biochemistry , chemistry , ubiquitin , ddb1 , dna , gene
The proto‐oncoprotein Hdm2 is a member of the RING finger‐type family of ubiquitin–protein ligases E3. The RING finger domain is assumed to mediate the specific interaction of an E3 with its cognate ubiquitin‐conjugating enzyme E2, which catalyzes the covalent attachment of ubiquitin to substrate proteins. In addition, the RING finger domain of Hdm2 is involved in Hdm2 homooligomer formation and has the capacity to bind to RNA in a sequence‐specific manner. Here we report that interaction with nucleic acids interferes with both Hdm2/Hdm2 complex formation and auto‐ubiquitination of Hdm2 in vitro. Furthermore, although binding of Hdm2 to the tumor suppressor p53 is not inhibited by nucleic acids, Hdm2‐mediated ubiquitination of p53 is significantly decreased. Taken together, these results provide the first example of an E3 whose activity can be regulated by direct interaction with nucleic acids.