Functional regulation of FEZ1 by the U-box-type ubiquitin ligase E4B contributes to neuritogenesis

Fumihiko Okumura, Shigetsugu Hatakeyama, Masaki Matsumoto, Takumi Kamura, Keiichi I. Nakayama

研究成果: ジャーナルへの寄稿学術誌査読

46 被引用数 (Scopus)


E4B (also known as UFD2a) is a mammalian homolog of Saccharomyces cerevisiae Ufd2, which was originally described as a ubiquitin chain assembly factor (E4). E4B is a U-box-type ubiquitin-protein isopeptide ligase (E3) and likely functions as either an E3 or an E4. With a yeast two-hybrid screen, we have now identified FEZ1 (fasciculation and elongation protein zeta 1) as a protein that interacts with E4B. FEZ1 is implicated in neuritogenesis when phosphorylated by protein kinase Cζ (PKCζ). Interaction between E4B and FEZ1 in mammalian cells was enhanced by coexpression of constitutively active PKCζ. E4B mediated the polyubiquitylation of FEZ1 but did not affect its intracellular stability, suggesting that such modification of FEZ1 is not a signal for its proteolysis. Polyubiquitylation of FEZ1 by E4B required Lys 27 of ubiquitin. Expression of a dominant-negative mutant of E4B in rat pheochromocytoma PC12 cells resulted in inhibition of neurite extension induced either by nerve growth factor or by coexpression of FEZ1 and constitutively active PKCζ. These findings indicate that E4B serves as a ubiquitin ligase for FEZ1 and thereby regulates its function but not its degradation.

ジャーナルJournal of Biological Chemistry
出版ステータス出版済み - 12月 17 2004

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学


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