Necdin-related MAGE proteins differentially interact with the E2F1 transcription factor and the p75 neurotrophin receptor.

Necdin is a growth suppressor expressed predominantly in postmitotic neurons and implicated in their terminal differentiation. Necdin shows a moderate homology to the MAGE family proteins, the functional roles of which are largely unknown. Human genes encoding necdin, MAGEL2 (necdin-like 1), and MAGE-G1 (necdin-like 2) are located in proximal chromosome 15q, a region associated with neurodevelopmental disorders such as Prader-Willi syndrome, Angelman syndrome, and autistic disorder. The necdin and MAGEL2 genes are subjected to genomic imprinting and suggested to be involved in the etiology of Prader-Willi syndrome. In this study, we compared biochemical and functional characteristics of murine orthologs of these necdin-related MAGE proteins. The colony formation and bromodeoxyuridine incorporation analyses revealed that necdin and MAGE-G1, but not MAGEL2, induced growth arrest. Necdin and MAGE-G1 interacted with the transcription factor E2F1 via its transactivation domain, repressed E2F1-dependent transcription, and antagonized E2F1-induced apoptosis of N1E-115 neuroblastoma cells. In addition, necdin and MAGE-G1 interacted with the p75 neurotrophin receptor via its distinct intracellular domains. In contrast, MAGEL2 failed to bind to these necdin interactors, suggesting that MAGEL2 has no necdin-like function in developing brain. Overexpression of p75 translocated necdin and MAGE-G1 in the proximity of the plasma membrane and reduced their association with E2F1 to facilitate E2F1-induced death of neuroblastoma cells. These results suggest that necdin and MAGE-G1 target both E2F1 and p75 to regulate cell viability during brain development.
AuthorsKen-ichiro Kuwako, Hideo Taniura, Kazuaki Yoshikawa
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 3 Pg. 1703-12 (Jan 16 2004) ISSN: 0021-9258 [Print] United States
PMID14593116 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Neoplasm
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2f1 protein, mouse
  • MAGEL2 protein, human
  • Magel2 protein, mouse
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Proteins
  • RNA, Messenger
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor
  • Transcription Factors
  • necdin
  • Animals
  • Antigens, Neoplasm
  • Apoptosis
  • Brain (metabolism)
  • Cell Cycle Proteins
  • Cell Division
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Mice
  • Mice, Inbred ICR
  • Nerve Tissue Proteins (physiology)
  • Nuclear Proteins (physiology)
  • Precipitin Tests
  • Protein Transport
  • Proteins (chemistry, physiology)
  • RNA, Messenger (analysis)
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor (chemistry, physiology)
  • Transcription Factors (chemistry, physiology)

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