Lessons from p53 in non-mammalian models

Lu, Wan Jin; Abrams, John

doi:10.1038/sj.cdd.4401922

Cited by 48 publications

(47 citation statements)

References 33 publications

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“…2), and virtually all cancers either harbor mutations in the p53 gene or have functionally inactivated p53 via other key pathway components (Junttila and Evan, 2009). Three p53 family members exist in fish, amphibians and mammals: p53, p63 (Trp63) and p73 (Trp73) (Lu and Abrams, 2006), although to date only one p53 member has been identified in urodeles (Villiard et al, 2007). Although all three can each induce growth arrest and apoptosis, p53 is the primary tumor suppressor.…”

Section: P53mentioning

confidence: 99%

Tumor suppressors: enhancers or suppressors of regeneration?

Pomerantz

Blau

2013

Development

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SummaryTumor suppressors are so named because cancers occur in their absence, but these genes also have important functions in development, metabolism and tissue homeostasis. Here, we discuss known and potential functions of tumor suppressor genes during tissue regeneration, focusing on the evolutionarily conserved tumor suppressors pRb1, p53, Pten and Hippo. We propose that their activity is essential for tissue regeneration. This is in contrast to suggestions that tumor suppression is a trade-off for regenerative capacity. We also hypothesize that certain aspects of tumor suppressor pathways inhibit regenerative processes in mammals, and that transient targeted modification of these pathways could be fruitfully exploited to enhance processes that are important to regenerative medicine.

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Section: P53mentioning

confidence: 99%

Tumor suppressors: enhancers or suppressors of regeneration?

Pomerantz

Blau

2013

Development

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“…A protein that activates the apoptotic response after irradiation is DmP53, the fly homolog of the product of the tumour suppressor gene p53 (reviewed by Lu and Abrams, 2006). Flies mutant for Dmp53 show very little apoptosis response to X-rays (Lee et al, 2003, Sogame et al, 2003 and similarly, over-expression of a dominant negative form of Dmp53 also inhibits response to irradiation (Brodsky et al, 2000, Ollmann et al, 2000.…”

Section: Genes Involved In the Apoptotic Stress Responsementioning

confidence: 99%

Apoptosis in Drosophila: compensatory proliferation and undead cells

Martín¹,

Pérez-Garijo²,

Morata³

2009

Int. J. Dev. Biol.

129

136

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Apoptosis (programmed cell death) is a conserved process in all animals, used to eliminate damaged or unwanted cells after stress events or during normal development to sculpt larval or adult structures. In Drosophila, it is known that stress events such as irradiation or heat shock give rise to high apoptotic levels which remove more than 50% of cells in imaginal discs. However, the surviving cells are able to restore normal size and pattern, indicating that they undergo additional proliferation. This "compensatory proliferation" is still poorly understood. One widely used method to study the properties of apoptotic cells is to keep them alive by expressing in them the baculoviral protein P35, which blocks the activity of the effector caspases. These "undead" cells acquire special features, such as the emission of the growth signals Dpp and Wg, changes in cellular morphology and induction of proliferation in neighbouring cells. Here, we review the various methods used in Drosophila to block apoptosis and its consequences, and focus on the generation and properties of undead cells in the wing imaginal disc. We describe their effects in epithelial architecture and growth in some detail, and discuss the possible relationship between undead cells and compensatory proliferation.

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“…A central focus of p53 research seeks to understand how this protein family integrates pathologic stimuli and functions to specify adaptive (or maladaptive) cellular responses. In mammals, p53 restrains cell growth by halting proliferation and/or inducing apoptosis but, in Drosophila and in Caenorhabditis elegans, the p53 ortholog influences apoptosis without exerting significant effects upon cell cycle progression (reviewed in Lu and Abrams, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…A primary mode of p53 action operates to regulate target genes at the level of transcription and, hence, a compelling focus of cancer research is driven by efforts to understand the downstream targets of p53 (reviewed in Lu and Abrams (2006); and see Supplementary Table S5). In many cases, regulated expression of downstream genes is context-specific and whether there exists a 'generic' p53program that drives apoptosis in all cells is not known.…”

Section: Introductionmentioning

confidence: 99%

p53 directs focused genomic responses in Drosophila

et al. 2007

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p53 is a fundamental determinant of cancer susceptibility and other age-related pathologies. Similar to mammalian counterparts, Drosophila p53 integrates stress signals and elicits apoptotic responses that maintain genomic stability. To illuminate core-adaptive functions controlled by this gene family, we examined the Drosophila p53 regulatory network at a genomic scale. In development, the absence of p53 impacted constitutive expression for a surprisingly broad scope of genes. By contrast, stimulusdependent responses governed by Drosophila p53 were limited in scope. The vast majority of stress responders were induced and p53 dependent (RIPD) genes. The signature set of 29 'high stringency' RIPD genes identified here were enriched for intronless loci, with a non-uniform distribution that includes a recently evolved cluster unique to Drosophila melanogaster. Two RIPD genes, with known and unknown biochemical activities, were functionally examined. One RIPD gene, designated XRP1, maintains genome stability after genotoxic challenge and prevents cell proliferation upon induced expression. A second gene, RnrL, is an apoptogenic effector required for caspase activation in a model of p53-dependent killing. Together, these studies identify ancient and convergent features of the p53 regulatory network.

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Lessons from p53 in non-mammalian models

Cited by 48 publications

References 33 publications

Tumor suppressors: enhancers or suppressors of regeneration?

Tumor suppressors: enhancers or suppressors of regeneration?

Apoptosis in Drosophila: compensatory proliferation and undead cells

p53 directs focused genomic responses in Drosophila

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