Functional domains of necdin for protein-protein interaction, nuclear matrix targeting, and cell growth suppression.

Abstract:

:Necdin is a growth suppressor expressed predominantly in postmitotic neurons. The necdin gene is involved in the etiology of the genomic imprinting-associated neurodevelopmental disorder Prader-Willi syndrome and belongs to the MAGE gene family. All the MAGE family proteins contain a large homology domain termed the MAGE homology domain (MHD). We here characterize the regions of necdin required for the protein-protein interaction, nuclear matrix targeting, and cell growth suppression. The region including entire MHD (amino acids 116-280) of necdin was required for its interaction with p53, while the regions amino acids 144-184 and 191-222 within the MHD were required for both the nuclear matrix targeting and the cell growth suppression of osteosarcoma SAOS-2 cells. The amino-terminal proline-rich acidic region (amino acids 60-100) was also necessary for cell growth suppression. Tetracycline-regulatable overexpression of necdin induced growth arrest of SAOS-2 cells in a reversible manner, and the necdin-overexpressing cells showed a large, flattened morphology with double nuclei. In contrast, a necdin mutant lacking amino acids 191-222 did not induce such changes. These findings suggest that different functions of necdin are mediated via its distinct domains.

journal_name

J Cell Biochem

authors

Taniura H,Kobayashi M,Yoshikawa K

doi

10.1002/jcb.20345

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

804-15

issue

4

eissn

0730-2312

issn

1097-4644

journal_volume

94

pub_type

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