The anaphase promoting complex induces substrate degradation during neuronal differentiation

Dympna Harmey, Anthony Smith, Scott Simanski, Carole Zaki Moussa, Nagi Ayad

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The anaphase promoting complex (APC) is an E3 ubiquitin ligase required for the metaphase-to-anaphase transition and mitotic exit. However, APC also plays roles in G1, where it is regulated by Cdh1, and APC activity has also been detected in differentiated and non-proliferating cells, suggesting that it may play roles outside the cell cycle. Here, we report that disrupting APCCdh1 activity inhibits neurite outgrowth of both PC12 pheochromocytoma cells and primary cerebellar granule cells. APCCdh1 activity dramatically increases as PC12 cells differentiate in response to nerve growth factor. Furthermore, a key target degraded by APCCdh1 following nerve growth factor treatment is the F-box protein Skp2, and APCCdh1-mediated destruction of Skp2 is essential for proper terminal differentiation of neuronal precursors.

Original languageEnglish
Pages (from-to)4317-4323
Number of pages7
JournalJournal of Biological Chemistry
Volume284
Issue number7
DOIs
StatePublished - Feb 13 2009
Externally publishedYes

Fingerprint

Anaphase-Promoting Complex-Cyclosome
PC12 Cells
Nerve Growth Factor
Degradation
Substrates
F-Box Proteins
Anaphase
Ubiquitin-Protein Ligases
Pheochromocytoma
Metaphase
Cell Cycle
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

The anaphase promoting complex induces substrate degradation during neuronal differentiation. / Harmey, Dympna; Smith, Anthony; Simanski, Scott; Moussa, Carole Zaki; Ayad, Nagi.

In: Journal of Biological Chemistry, Vol. 284, No. 7, 13.02.2009, p. 4317-4323.

Research output: Contribution to journalArticle

Harmey, Dympna ; Smith, Anthony ; Simanski, Scott ; Moussa, Carole Zaki ; Ayad, Nagi. / The anaphase promoting complex induces substrate degradation during neuronal differentiation. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 7. pp. 4317-4323.
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