U Box Proteins as a New Family of Ubiquitin-Protein Ligases*

By S. Hatakeyama, M. Yada, M. Matsumoto, N. Ishida, K. Nakayama. Journal of Biological Chemistry, 2001

609 citations recorded by the source corpus.

The U box is a domain of ∼70 amino acids that is present in proteins from yeast to humans. The prototype U box protein, yeast Ufd2, was identified as a ubiquitin chain assembly factor that cooperates with a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and a ubiquitin-protein ligase (E3) to catalyze ubiquitin chain formation on artificial substrates. E3 enzymes are thought to determine the substrate specificity of ubiquitination and have been classified into two families, the HECT and RING finger families. Six mammalian U box proteins have now been shown to mediate polyubiquitination in the presence of E1 and E2 and in the absence of E3. These U box proteins exhibited different specificities for E2 enzymes in this reaction. Deletion of the U box or mutation of conserved amino acids within it abolished ubiquitination activity. Some U box proteins catalyzed polyubiquitination by targeting lysine residues of ubiquitin other than lysine 48, which is utilized by HECT and RING finger E3 enzymes for polyubiquitination that serves as a signal for proteolysis by the 26 S proteasome. These data suggest that U box proteins constitute a third family of E3 enzymes and that E4 activity may reflect a specialized type of E3 activity.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a0eaf3b0b0b8aba68043b6cd6b4f7aab1142dc5f

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Citations in the corpus

• Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression (2004, background): “3 to 3-fold) were observed in mRNAs for the ubiquitination factor E4B, which may act in combination with an E3 to increase the efficiency of Ub conjugation to proteins (36).”
• The Ubiquitin-Proteasome Pathway and Plant Development (2004, background): “There is evidence in animal systems that U-box E3s interact with chaperones to targetmisfolded proteins for degradation (Hatakeyama and Nakayama, 2003).”
• HECT and RING finger families of E3 ubiquitin ligases at a glance (2012, background): “The U-box creates an E2 binding surface that resembles a RING finger, but lacks Zn2+-coordinating sites and, instead, contains stabilizing hydrogen bonds and salt bridges (Aravind and Koonin, 2000; Hatakeyama et al., 2001; Pringa et al., 2001).”
• The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. (2002, background): “, target their substrates directly (153).”
• Ubiquitin: structures, functions, mechanisms. (2004, background): “found to abolish ligase activity [105] even though the mutations do not destabilize the domain’s overall conformation [110].”