Mitochondrial p32 is a critical mediator of ARF-induced apoptosis.

@article{Itahana2008MitochondrialPI,
  title={Mitochondrial p32 is a critical mediator of ARF-induced apoptosis.},
  author={Koji Itahana and Yanping Zhang},
  journal={Cancer cell},
  year={2008},
  volume={13 6},
  pages={
          542-53
        }
}

Figures from this paper

ARF in the mitochondria: The last frontier?

It is shown that ARF interacts with the mitochondrial protein p32/C1QBP and that the interaction is critical in order for ARF to localize to the mitochondria and induce apoptosis, and hence ARF's pro-apoptotic function can be interrupted by human cancer-derived mutations in exon2 of the p14ARF-p16INK4a gene locus.

Interaction of the ARF tumor suppressor with cytosolic HSP70 contributes to its autophagy function

The premise that 2-phenylethynesulfonamide (PES) may show preferential cytotoxicity to advanced stage cancers is supported, as high levels of ARF are characteristic of tumor cells with enhanced MAPK signaling and advanced stage; therefore, these data support the premise.

A short acidic motif in ARF guards against mitochondrial dysfunction and melanoma susceptibility.

It is shown that, in human melanocytes, ARF is cytoplasmic, constitutively expressed, and required for maintaining low steady-state levels of superoxide under conditions of mitochondrial dysfunction.

Regulation of p14ARF tumor suppressor activities and functions

The role of endogenously expressed ARF protein in some tumor and stabilized cell lines is explored by knocking down ARF expression by siRNA and the results suggest that ARF might have a pro-survival role depending on cellular context.

A conserved domain in exon 2 coding for the human and murine ARF tumor suppressor protein is required for autophagy induction

It is shown that whereas full-length ARF can induce autophagy, the combined data suggest that smARF instead induces mitophagy (selectiveAutophagy of mitochondria), thus potentially resolving some confusion regarding the role of these variants.

Amino terminal hydrophobic import signals target the p14ARF tumor suppressor to the mitochondria

It is suggested that once this hydrophobic pocket is exposed, possibly in a stimulus-dependent manner, it accelerates the mitochondrial import of p14ARF, which allows the interaction of p 14ARF with mitochondrial proteins, including p32 and enables p53-independent cell death.

Mimicking p14ARF Phosphorylation Influences Its Ability to Restrain Cell Proliferation

It is shown for the first time that p14ARF is a PKC target and proposed that phosphorylation of ARF in both immortalized and tumor cell lines could be a mechanism to escape ARF surveillance following proliferative and oncogenic stress.

ARF Induces Autophagy by Virtue of Interaction with Bcl-xl*

The combined data support the premise that ARF induces autophagy in a p53-independent manner in part by virtue of its interaction with Bcl-xl, and indicate that silencing p53 leads to high levels of ARF and increasedAutophagy.

p53, ARF, and the Control of Autophagy

The evidence for a role of p53 and ARF in autophagy, the role of this pathway in cancer, and what questions remain to be answered are outlined.

Small mitochondrial Arf (smArf) protein corrects p53-independent developmental defects of Arf tumor suppressor-deficient mice

Missing potent p53-dependent tumor suppressor activity, p15smArf can surprisingly act independently of p19Arf to correct the focal developmental defects of Arf-null mice, which are prone to tumor development and male germ cells exhibit defects in meiotic maturation and sperm production.
...

References

SHOWING 1-10 OF 67 REFERENCES

A short mitochondrial form of p19ARF induces autophagy and caspase-independent cell death.

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.

E1A signaling to p53 involves the p19(ARF) tumor suppressor.

Reintroduction of p19(ARF) functions as part of a p53-dependent failsafe mechanism to counter uncontrolled proliferation and may contribute to E1A's ability to enhance radio- and chemosensitivity.

The autophagic inducer smARF interacts with and is stabilized by the mitochondrial p32 protein

The interaction with p32 provides a means of specifically regulating the expression of the recently identified autophagic inducer, smARF, and adds yet another layer of complexity to the multifaceted regulation of the ARF gene.

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.

Cooperative Signals Governing ARF-Mdm2 Interaction and Nucleolar Localization of the Complex

The results suggest that ARF binding to Mdm2 induces a conformational change that facilitates nucleolar import of the ARF-Mdm2 complex and p53-dependent cell cycle arrest.

Bak functionally complements for loss of Bax during p14ARF-induced mitochondrial apoptosis in human cancer cells

It is shown that p14ARF induces breakdown of the mitochondrial membrane potential and cytochrome c release before triggering caspase-9- and caspases-3/7-like activities in p53/Bax-deficient DU145 prostate cancer cells expressing wild-type Bak.
...