The Prader-Willi syndrome protein necdin interacts with the E1A-like inhibitor of differentiation EID-1 and promotes myoblast differentiation.

Abstract

Proliferation and differentiation of muscle precursors are controlled by the activation of muscle-specific genes and inactivation of inhibitors of differentiation. Necdin is a multi-functional protein that is up-regulated during neural and myogenic differentiation. Necdin facilitates cell cycle exit and differentiation during development, but the role of necdin in embryonic myogenesis has not been described. In a cytoplasmic two-hybrid screen, we identified a novel interaction between necdin and the E1A-like inhibitor of differentiation (EID-1). EID-1 inhibits transcriptional activation of genes required for myogenic differentiation, and is degraded in myoblasts upon cell cycle exit. In a transactivation assay, necdin had no direct effect on myoD-responsive promoters in the presence of MyoD, but necdin did relieve the EID-1-dependent inhibition of these same promoters. In vivo, a normal number of MyoD-expressing myoblasts was present in primary embryonic limb bud cultures from mouse embryos with congenital necdin deficiency. In contrast, the number of myosin heavy chain-expressing myotubes in differentiating limb bud cultures cultured for 5 days was reduced compared with cultures from wild-type littermate controls. In the presence of necdin, steady-state levels of EID-1 were increased and the half-life of EID-1 was extended, and EID-1 was re-localized from the nucleus to the cytoplasm when necdin was co-expressed in transfected cells. Collectively, these data are consistent with a model whereby necdin promotes myoblast differentiation at least in part by relieving the inhibitory effect of EID-1.

• Authors: Jason R Bush, Rachel Wevrick
• Journal: Differentiation; research in biological diversity (Differentiation) Vol. 76 Issue 9 Pg. 994-1005 (Nov 2008) ISSN: 1432-0436 [Electronic] England
• PMID: 18557765 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• EID1 protein, human
• Nerve Tissue Proteins
• Nuclear Proteins
• Repressor Proteins
• necdin

Topics

• Animals
• Cell Cycle Proteins
• Cell Differentiation
• Cell Nucleus (metabolism)
• Cells, Cultured
• Cytoplasm (metabolism)
• Embryo, Mammalian (metabolism)
• Fluorescent Antibody Technique
• Humans
• Mice
• Mice, Transgenic
• Myoblasts (cytology, metabolism)
• Nerve Tissue Proteins (metabolism)
• Nuclear Proteins (genetics, metabolism)
• Prader-Willi Syndrome (metabolism)
• Repressor Proteins (genetics, metabolism)
• Two-Hybrid System Techniques