Format

Send to

Choose Destination
Oncogene. 2002 Sep 19;21(42):6403-12.

A key role of the hSNF5/INI1 tumour suppressor in the control of the G1-S transition of the cell cycle.

Author information

1
INSERM U509, Laboratoire de Pathologie Mol├ęculaire des Cancers, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.

Abstract

The hSNF5/INI1 gene encodes a member of the SWI/SNF chromatin remodelling complexes. It was recently identified as a tumour suppressor gene mutated in sporadic and hereditary Malignant Rhabdoid Tumours (MRT). However, the role of hSNF5/INI1 loss-of-function in tumour development is still unknown. Here, we show that the ectopic expression of wild-type hSNF5/INI1, but not that of truncated versions, leads to a cell cycle arrest by inhibiting the entry into S phase of MRT cells. This G1 arrest is associated with down-regulation of a subset of E2F targets including cyclin A, E2F1 and CDC6. This arrest can be reverted by coexpression of cyclin D1, cyclin E or viral E1A, whereas it cannot be counteracted by pRB-binding deficient E1A mutants. Moreover, hSNF5/INI1 is not able to arrest cells lacking a functional pRB. These observations suggest that the hSNF5/INI1-induced G1 arrest is dependent upon the presence of a functional pRB. However, the observation that a constitutively active pRB can efficiently arrest MRT cells indicates that hSNF5/INI1, at the difference of the ATPase subunits of the SWI/SNF complex, is dispensable for pRB function. Altogether, these data show that hSNF5/INI1 is a potent regulator of the entry into S phase, an effect that may account for its tumour suppressor role.

PMID:
12226744
DOI:
10.1038/sj.onc.1205841
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center