Necdin, a postmitotic neuron-specific growth suppressor, interacts with viral transforming proteins and cellular transcription factor E2F1.

Necdin is a nuclear protein expressed in virtually all postmitotic neurons, and ectopic expression of this protein strongly suppresses the proliferation of NIH3T3 cells. Simian virus 40 large T antigen targets both p53 and the retinoblastoma protein (Rb) for cellular transformation. By analogy with the interactions of the large T ...
antigen with these nuclear growth suppressors, we examined the ability of necdin to bind to the large T antigen. Necdin was co-immunoprecipitated with the large T antigen from the nuclear extract of necdin cDNA-transfected COS-1 cells. Yeast two-hybrid and in vitro binding analyses revealed that necdin bound to an amino-terminal region of the large T antigen, which encompasses the Rb-binding domain. Moreover, necdin bound to adenovirus E1A, another viral oncoprotein that forms a specific complex with Rb. We then examined the ability of necdin to bind to the transcription factor E2F1, a cellular Rb-binding factor involved in cell-cycle progression. Intriguingly, necdin, like Rb, bound to a carboxyl-terminal domain of E2F1, and repressed E2F-dependent transactivation in vivo. In addition, necdin suppressed the colony formation of Rb-deficient SAOS-2 osteosarcoma cells. These results suggest that necdin is a postmitotic neuron-specific growth suppressor that is functionally similar to Rb.
Mesh Terms:
3T3 Cells, Animals, Antigens, Polyomavirus Transforming, COS Cells, Carrier Proteins, Cell Cycle Proteins, Cell Division, Cell Transformation, Viral, DNA-Binding Proteins, E2F Transcription Factors, E2F1 Transcription Factor, Mice, Nerve Tissue Proteins, Nuclear Proteins, Protein Binding, Retinoblastoma Protein, Retinoblastoma-Binding Protein 1, Transcription Factor DP1, Transcription Factors, Viral Proteins
J. Biol. Chem.
Date: Jan. 09, 1998
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