Nucleolar p19ARF unlike mitochondrial smARF is incapable of inducing p53-independent autophagy

Reef, Sharon; Kimchi, Adi

doi:10.4161/auto.6691

Cited by 17 publications

(14 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As a result, cell lines overexpressing smARF are more sensitive to the induction of autophagy and senescence caused by starvation or hydrogen peroxide (Pimkina et al, 2009). In contrast, expression of nucleolar ARF does not confer a similar effect (Reef and Kimchi, 2008). These observations indicate that smARF may link autophagy to senescence but whether this applies also in response to DNA damage remains to be determined.…”

Section: Functional Outcomes Of the Ddr – Autophagy Axismentioning

confidence: 99%

DNA Damage Response and Autophagy: A Meaningful Partnership

2016

View full text Add to dashboard Cite

Autophagy and the DNA damage response (DDR) are biological processes essential for cellular and organismal homeostasis. Herein, we summarize and discuss emerging evidence linking DDR to autophagy. We highlight published data suggesting that autophagy is activated by DNA damage and is required for several functional outcomes of DDR signaling, including repair of DNA lesions, senescence, cell death, and cytokine secretion. Uncovering the mechanisms by which autophagy and DDR are intertwined provides novel insight into the pathobiology of conditions associated with accumulation of DNA damage, including cancer and aging, and novel concepts for the development of improved therapeutic strategies against these pathologies.

show abstract

Section: Functional Outcomes Of the Ddr – Autophagy Axismentioning

confidence: 99%

DNA Damage Response and Autophagy: A Meaningful Partnership

2016

View full text Add to dashboard Cite

show abstract

“…The pro-autophagic effect of short mitochondrial ARF is known to be enhanced by the mitochondrial p32 protein that stabilizes short mitochondrial ARF but not the full-length ARF (Reef et al, 2007). It has been shown that the full-length ARF that normally resides in the nucleolus is incapable of inducing p53-independent autophagy (Reef and Kimchi, 2008).…”

Section: V12mentioning

confidence: 99%

The autophagic paradox in cancer therapy

et al. 2011

View full text Add to dashboard Cite

Autophagy, hallmarked by the formation of doublemembrane bound organelles known as autophagosomes, is a lysosome-dependent pathway for protein degradation. The role of autophagy in carcinogenesis is context dependent. As a tumor-suppressing mechanism in earlystage carcinogenesis, autophagy inhibits inflammation and promotes genomic stability. Moreover, disruption of autophagy-related genes accelerates tumorigenesis in animals. However, autophagy may also act as a prosurvival mechanism to protect cancer cells from various forms of cellular stress. In cancer therapy, adaptive autophagy in cancer cells sustains tumor growth and survival in face of the toxicity of cancer therapy. To this end, inhibition of autophagy may sensitize cancer cells to chemotherapeutic agents and ionizing radiation. Nevertheless, in certain circumstances, autophagy mediates the therapeutic effects of some anticancer agents. Data from recent studies are beginning to unveil the apparently paradoxical nature of autophagy as a cellfate decision machinery. Taken together, modulation of autophagy is a novel approach for enhancing the efficacy of existing cancer therapy, but its Janus-faced nature may complicate the clinical development of autophagy modulators as anticancer therapeutics.

show abstract

“…66 Yet, a further detailed study established that nucleolar localized full-length p19ARF, unlike the mitochondrial smARF, is incapable of inducing p53-independent autophagy. 67 An additional study suggested that human p14ARF also localizes to the outer membrane of mitochondria where it binds Bcl-2/X L , thereby reducing the latter's association with Beclin 1, 68 although it is unclear how an interaction at the mitochondria affects the ER-localized Bcl-2/ Beclin 1 complex. Oncogene expression results in the induction of both full-length p19ARF and smARF, 64 suggesting that smARF's contribution to autophagy is more prominent upon specific cell signals.…”

Section: Cross-talk Between Autophagy and Apoptosismentioning

confidence: 99%

Life and death partners: apoptosis, autophagy and the cross-talk between them

et al. 2009

View full text Add to dashboard Cite

It is not surprising that the demise of a cell is a complex well-controlled process. Apoptosis, the first genetically programmed death process identified, has been extensively studied and its contribution to the pathogenesis of disease well documented. Yet, apoptosis does not function alone to determine a cell's fate. More recently, autophagy, a process in which de novo-formed membrane-enclosed vesicles engulf and consume cellular components, has been shown to engage in a complex interplay with apoptosis. In some cellular settings, it can serve as a cell survival pathway, suppressing apoptosis, and in others, it can lead to death itself, either in collaboration with apoptosis or as a back-up mechanism when the former is defective. The molecular regulators of both pathways are inter-connected; numerous death stimuli are capable of activating either pathway, and both pathways share several genes that are critical for their respective execution. The cross-talk between apoptosis and autophagy is therefore quite complex, and sometimes contradictory, but surely critical to the overall fate of the cell. Furthermore, the crosstalk is a key factor in the outcome of death-related pathologies such as cancer, its development and treatment. Autophagy, a process long known to provide a survival advantage to cells undergoing nutrient deprivation or other stresses, has also been more recently linked to the actual death process itself. Thus apoptosis is not the sole means by which the cell can undergo a genetically programmed regulated process by which it undergoes self-elimination. Cell death can occur by several mechanisms and the phenotypic changes that accompany cell death can vary depending on the stimulus and cell setting. In any given death scenario, the cell decides which pathway to use, depending on the nature of the stimulus and the particulars of the cell environment. Furthermore, apoptosis and autophagy are not mutually exclusive pathways. They have been shown to act in synergy and also to counter each other. They share many of the same molecular regulators. In a clinical setting, one cannot predict the outcome of inhibition or activation of one death program without considering the effect on the other. This review will focus on the cross-talk between the autophagic and apoptotic pathways, with an analysis of how this may affect the clinical applications of death suppression/activation to cancer. The process of necrosis, the third means by which the cell can undergo a genetically programmed self-elimination, will not be discussed in detail. Although not intended to provide an exhaustive summary of the recent literature, the discussion will include salient experimental results as examples of the different facets of the apoptosis/autophagy interplay.An issue that has been raised and discussed in the literature is that in many cell settings, autophagy accompanies, rather than causes, cell death. 1 This argument is based on the fact that many studies that claim autophagic cell death prove that autophagy occurs, and that ...

show abstract

Nucleolar p19ARF unlike mitochondrial smARF is incapable of inducing p53-independent autophagy

Cited by 17 publications

References 20 publications

DNA Damage Response and Autophagy: A Meaningful Partnership

DNA Damage Response and Autophagy: A Meaningful Partnership

The autophagic paradox in cancer therapy

Life and death partners: apoptosis, autophagy and the cross-talk between them

Contact Info

Product

Resources

About