Absence of p53-dependent apoptosis leads to UV radiation hypersensitivity, enhanced immunosuppression and cellular senescence

Tavana, Omid; Benjamin, Cara L.; Puebla-Osorio, Nahum; Sang, Mei; Ullrich, Stephen E.; Ananthaswamy, Honnavara N.; Zhu, Chengming

doi:10.4161/cc.9.16.12688

Cited by 53 publications

(35 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…40 Absence of p53-dependent apoptosis leads to cellular senescence. 41 However, the involvement of p53 in curcumin-induced apoptosis remains unclear. For example, curcumin has been shown to induce apoptosis in a p53-dependent manner in multiple cancer cell types, 11,14,42 and via a p53-independent mechanism in others.…”

Section: Discussionmentioning

confidence: 99%

Curcumin induces Apaf-1-dependent, p21-mediated caspase activation and apoptosis

et al. 2011

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Curcumin induces Apaf-1-dependent, p21-mediated caspase activation and apoptosis

et al. 2011

View full text Add to dashboard Cite

“…Mitochondrial fusion in response to cell stressors including inhibition of translation and UV irradiation requires mitochondrial scaffolding protein SLP-2 to support Opa1 fusion activity (Tondera et al, 2009) ( Figure 3 ). Though senescence was not a parameter of the Tondera et al study, the “stressors” utilized to achieve mitochondrial elongation have been used previously as modes of senescence induction (Chainiaux et al, 2002, Robles and Adami, 1998, Tavana et al, 2010). Therefore, understanding the role of SLP-2 in the establishment of senescence would contribute to the role of mitochondrial elongation in senescence.…”

Section: Mitophagy and Senescence: Implications For Copd Pathogenesismentioning

confidence: 99%

Mitochondrial redox system, dynamics, and dysfunction in lung inflammaging and COPD

Lerner

Sundar

Rahman

2016

The International Journal of Biochemistry & Cell Biology

View full text Add to dashboard Cite

Myriad forms of endogenous and environmental stress will disrupt mitochondrial function by impacting critical processes in mitochondrial homeostasis such as mitochondrial redox system, oxidative phosphorylation, biogenesis, and mitophagy. External stressors that interfere with the steady state activity of mitochondrial functions are generally associated with an increase in reactive oxygen species, inflammatory response, and induction of cellular senescence (inflammaging) via mitochondrial damage associated molecular patterns (DAMPS) which are the key events in the pathogenesis of chronic obstructive pulmonary disease (COPD) and its exacerbations. In this review, we highlight the primary mitochondrial quality control mechanisms that are influenced by oxidative stress/redox system, including role of mitochondria during inflammation and cellular senescence, and how mitochondrial dysfunction contributes to the pathogenesis of COPD and its exacerbations via pathogenic stimuli.

show abstract

“…77 Also, mice harboring a hypomorphic mutant p53, R172P, a mutation that abrogates p53-mediated apoptosis while keeping cell cycle control intact, are more sensitive to ultraviolet light-induced skin inflammation than wild-type mice. 78 Finally, a significant proportion of tumor-prone p53-null mice (25%) die before tumor development from unresolved inflammation that results in abscesses, gastroenteritis, or myocarditis, 16,76 suggesting that the control of innate immune response is deregulated in these mice. 79 Consistent with the observations described above, we found that p53 is a general inhibitor of inflammation and that this activity is due to its antagonism of NF-κB (Figure 4).…”

Section: P53 As An Inhibitor Of Inflammationmentioning

confidence: 99%

Inflammation and p53: A Tale of Two Stresses

Gudkov

Gurova²,

Komarova³

2011

Genes & Cancer

178

145

View full text Add to dashboard Cite

Numerous observations indicate a strong link between chronic inflammation and cancer. This link is supported by substantial experimental evidence indicating mutual negative regulation of NF-κB, the major regulator of inflammation, and p53, the major tumor suppressor. This antagonistic relationship reflects the opposite principles of the physiological responses driven by these transcription factors, which act as sensors and mediators of intrinsic and extrinsic cell stresses, respectively. Constitutive activation of NF-κB, the underlying cause of chronic inflammation, is a common acquired characteristic of tumors. A variety of experimental methods have been used to demonstrate that constitutive activation of NF-κB reduces the tumor suppressor activity of p53, thereby creating permissive conditions for dominant oncogene-mediated transformation. Loss of p53 activity is also a characteristic of the majority of tumors and results in unleashed inflammatory responses due to loss of p53-mediated NF-κB suppression. On the other hand, in natural or pharmacological situations of enforced p53 activation, NF-κB activity, inflammation, and immune responses are reduced, resulting in different pathologies. It is likely that the chronic inflammation that is commonly acquired in various tissues of older mammals leads to general suppression of p53 function, which would explain the increased risk of cancer observed in aging animals and humans. Although the molecular mechanisms underlying reciprocal negative regulation of p53 and NF-κB remain to be deciphered, this phenomenon has important implications for pharmacological prevention of cancer and aging and for new approaches to control inflammation.

show abstract

Absence of p53-dependent apoptosis leads to UV radiation hypersensitivity, enhanced immunosuppression and cellular senescence

Cited by 53 publications

References 61 publications

Curcumin induces Apaf-1-dependent, p21-mediated caspase activation and apoptosis

Curcumin induces Apaf-1-dependent, p21-mediated caspase activation and apoptosis

Mitochondrial redox system, dynamics, and dysfunction in lung inflammaging and COPD

Inflammation and p53: A Tale of Two Stresses

Contact Info

Product

Resources

About