The<i>Caenorhabditis elegans ing-3</i>Gene Regulates Ionizing Radiation-Induced Germ-Cell Apoptosis in a p53-Associated Pathway

Luo, Jingjing; Shah, Sitar; Riabowol, Karl; Mains, Paul E.

doi:10.1534/genetics.107.080515

Cited by 23 publications

(26 citation statements)

References 65 publications

(92 reference statements)

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“…The worm homolog of the human SIRT1 histone deacetylase, which has been implicated in regulating transcriptional repression and aging also affects IR induced apoptosis (Greiss et al 2008a). Other such factors are the ING-3 transcription factor (Luo et al 2009) and components of the ceramide synthesis pathway have been shown to be required for DNA damage induced apoptosis (Deng et al 2008). At the moment these factors cannot be placed into a simple genetic or biochemical pathway and future studies will be required to mechanistically link these genes to apoptosis regulation.…”

Section: Phylogeny and Functionmentioning

confidence: 99%

Phylogeny and Function of the Invertebrate p53 Superfamily

Rutkowski¹,

Hofmann²,

Gartner³

2010

Cold Spring Harbor Perspectives in Biology

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The origin of the p53 superfamily predates animal evolution and first appears in unicellular Flagellates. Invertebrate p53 superfamily members appear to have a p63-like domain structure, which seems to be evolutionarily ancient. The radiation into p53, p63, and p73 proteins is a vertebrate invention. In invertebrate models amenable to genetic analysis p53 superfamily members mainly act in apoptosis regulation in response to genotoxic agents and do not have overt developmental functions. We summarize the literature on cnidarian and mollusc p53 superfamily members and focus on the function and regulation of Drosophila melanogaster and Caenorhabditis elegans p53 superfamily members in triggering apoptosis. Furthermore, we examine the emerging evidence showing that invertebrate p53 superfamily proteins also have functions unrelated to apoptosis, such as DNA repair, cell cycle checkpoint responses, compensatory proliferation, aging, autophagy, and innate immunity.T he vertebrate p53 family of proteins consists of three members, p53, p63, and p73. p53 has received considerable attention because of the fact that it is mutated in approximately 50% of all human cancers and plays an important role in protecting cells against DNA damage and cellular stressors. p63 and p73 on the other hand, seem to be less involved in tumorigenesis but play important roles in epithelial development and neurogenesis, respectively. p53 related sequences also exist in invertebrate species. We review the functional data on invertebrate p53 superfamily proteins, largely focusing on the model organisms, Caenorhabditis elegans and Drosophila melanogaster. Invertebrate p53 superfamily members act in apoptosis regulation in response to genotoxic agents and the deletion of invertebrate p53 superfamily proteins does not lead to overall developmental defects. Nevertheless, there is emerging evidence that invertebrate p53-like proteins also have functions unrelated to apoptosis.There has been a debate whether invertebrate p53 superfamily proteins are phylogenetically more related to vertebrate p53 or p63. Taking

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Section: Phylogeny and Functionmentioning

confidence: 99%

Phylogeny and Function of the Invertebrate p53 Superfamily

Rutkowski¹,

Hofmann²,

Gartner³

2010

Cold Spring Harbor Perspectives in Biology

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“…Cep-1 has a well-documented phenotype in worm germline apoptosis [68,69]. After exposing ing-3 (RNAi) C. elegans to 120Gy of IR, a strong suppression of programmed cell death was noted compared to wildtype animals, which showed approximately twice the number of apoptotic germ cells [70]. The embryonic death rate increased while the number of germ cell corpses in a cep-1 mutant decreased to similar extents as seen in ing-3 mutants.…”

Section: Ing3 Ablation In Caenorhabditis Elegansmentioning

confidence: 95%

Signaling Pathways of the ING Proteins in Apoptosis

Shah

Riabowol²

2009

CDT

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Members of the ING family of type II tumor suppressors reside in different chromatin regulatory complexes and are stoichiometeric members of histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes. It has been frequently observed that expressing ING proteins promotes apoptosis in both normal and transformed cells of different species. They have also been reported to either rely upon p53, or to add to its ability to promote programmed cell death (apoptosis) although whether ING proteins require p53 to induce apoptosis is now questionable based upon observations using knockout cell lines and animal models. Genetic studies in model organisms, and particularly in Caenorhabditis elegans, have identified different pathways involved in apoptosis during development, in the germ line and in response to various forms of stress including DNA damage. In this review we summarize structural features of the INGs and recent observations made in knockout models of Mus musculus and Caenorhabditis elegans that have helped to further clarify the functions of the ING proteins in biochemical pathways leading to apoptosis. Based upon these observations we propose a model for how ING proteins may act both independently and in concert with p53 to promote apoptosis.

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“…It was also shown to co-localize with chromatin and function in concert with the C. elegans p53 homolog, cep-1, to induce germ-cell apoptosis in response to ionizing radiation [160]. Accordingly, a cep-1 deletion allele decreased the number of γ-rays-induced germ-cell death to a similar extent as the loss of ING3 did.…”

Section: Ing3 and P53mentioning

confidence: 96%

“…Interestingly, depletion of the Caenorhabditis elegans homolog of ING3 gene with a considerable sequence identity to the human ING3 conferred a strong resistance to apoptosis following ionizing radiation from γ-rays [160]. It was also shown to co-localize with chromatin and function in concert with the C. elegans p53 homolog, cep-1, to induce germ-cell apoptosis in response to ionizing radiation [160].…”

Section: Ing3 and P53mentioning

confidence: 99%

Regulation of p53 by ING family members in suppression of tumor initiation and progression

Jafarnejad

2011

Cancer Metastasis Rev

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The INhibitor of Growth (ING) family is an evolutionarily conserved set of proteins, implicated in suppression of initiation and progression of cancers in various tissues. They promote cell cycle arrest, cellular senescence and apoptosis, participate in stress responses, regulate DNA replication and DNA damage responses, and inhibit cancer cell migration, invasion, and angiogenesis of the tumors. At the molecular level, ING proteins are believed to participate in chromatin remodeling and transcriptional regulation of their target genes. However, the best known function of ING proteins is their cooperation with p53 tumor suppressor protein in tumor suppression. All major isoforms of ING family members can promote the transactivition of p53 and the majority of them are shown to directly interact with p53. In addition, ING proteins are thought to interact with and modulate the function of auxiliary members of p53 pathway, such as MDM2, ARF , p300, and p21, indicating their widespread involvement in the regulation and function of this prominent tumor suppressor pathway. It seems that p53 pathway is the main mechanism by which ING proteins exert their functions. Nevertheless, regulation of other pathways which are not relevant to p53, yet important for tumorigenesis such as TGF-β and NF-κB, by ING proteins is also observed. This review summarizes the current understanding of the mutual interactions and cooperation between different members of ING family with p53 pathway and implications of this cooperation in the suppression of cancer initiation and progression.

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TheCaenorhabditis elegans ing-3Gene Regulates Ionizing Radiation-Induced Germ-Cell Apoptosis in a p53-Associated Pathway

Cited by 23 publications

References 65 publications

Phylogeny and Function of the Invertebrate p53 Superfamily

Phylogeny and Function of the Invertebrate p53 Superfamily

Signaling Pathways of the ING Proteins in Apoptosis

Regulation of p53 by ING family members in suppression of tumor initiation and progression

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