ARF Promotes MDM2 Degradation and Stabilizes p53: ARF-INK4a Locus Deletion Impairs Both the Rb and p53 Tumor Suppression Pathways

@article{Zhang1998ARFPM,
  title={ARF Promotes MDM2 Degradation and Stabilizes p53: ARF-INK4a Locus Deletion Impairs Both the Rb and p53 Tumor Suppression Pathways},
  author={Yanping Zhang and Yue Xiong and Wendell G. Yarbrough},
  journal={Cell},
  year={1998},
  volume={92},
  pages={725-734}
}

Figures from this paper

ARF promotes accumulation of retinoblastoma protein through inhibition of MDM2

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Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2.

Overexpression of p19(ARF) in wild type or ARF-null mouse embryo fibroblasts increases the half-life of p53 from 15 to approximately 75 min, correlating with an increased p53-dependent transcriptional response and growth arrest.

Modific ation of mdmx by ubiquitination and sumoylation

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P19(ARF) stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2.

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It is shown here that coexpression of p19(ARF) blocks the nucleo-cytoplasmic shuttling of Mdm2, suggesting that MDM2 might be exported through the nucleolus and p19-ARF could inhibit the nuclear export of Mdn2 by tethering Mdm1 in the nucleolia.

Ribosomal Protein L11 Negatively Regulates Oncoprotein MDM2 and Mediates a p53-Dependent Ribosomal-Stress Checkpoint Pathway

It is shown that the functional consequence of L11-HDM2 association results in the prevention of HDM2-mediated p53 ubiquitination and degradation, subsequently restoring p53-mediated transactivation, accumulating p21 protein levels, and inducing a p 53-dependent cell cycle arrest by canceling the inhibitory function of HDm2.

Defining the Role of CtBP2 in p53-Independent Tumor Suppressor Function of ARF: A Dissertation

Evidence suggests that ARF exerts both p53dependent and p53-independent tumor suppressor activity, and the antiapoptotic, metabolically regulated, transcriptional corepressor C-terminal binding protein 2 (CtBP2) has been identified as a specific target of ARF’s p53independent tumor suppression.

Human tumor suppressor ARF impedes S-phase progression independent of p53.

It is shown that ARF colocalizes with DNA replication protein A (RPA32) and that overexpression of ARF reduces the rate of DNA synthesis resulting in accumulation of an S-phase cell population and that Impediment ofDNA synthesis by ARF can occur and becomes more evident in the absence of p53.
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