A functional link between the tumour suppressors ARF and p33ING1.

Abstract:

:The ARF tumour suppressor protein plays a critical role in the activation of p53 in response to oncogenic stress. ARF can activate p53 through nucleolar sequestration of Mdm2. However, several lines of evidence indicate that this is not the only way of action of ARF, and alternative mechanisms must exist. p33ING1 is a putative tumour suppresor, which induces cell-cycle arrest and apoptosis in a p53-dependent manner. Here, we describe that ARF and p33ING1 can interact in vivo. We also show that the subcellular localization of ING1 can be modulated by ARF protein levels, causing a displacement from nuclear to nucleolar localization. Finally, the ability of p33ING1 to cause cell-cycle arrest and induction of p21CIP1, or Mdm2, is impaired in ARF-deficient primary mouse fibroblasts. Based on these observations, we propose that the interaction with p33ING1 represents a novel mechanism for the tumour suppression function of ARF.

journal_name

Oncogene

journal_title

Oncogene

authors

González L,Freije JM,Cal S,López-Otín C,Serrano M,Palmero I

doi

10.1038/sj.onc.1209526

subject

Has Abstract

pub_date

2006-08-24 00:00:00

pages

5173-9

issue

37

eissn

0950-9232

issn

1476-5594

pii

1209526

journal_volume

25

pub_type

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