Daxx-like Protein of Drosophila Interacts with Dmp53 and Affects Longevity and Ark mRNA Level

Bodai, László; Pardi, Norbert; Újfaludi, Zsuzsanna; Bereczki, Orsolya; Komonyi, Orbán; Bálint, Éva; Boros, Imre

doi:10.1074/jbc.m705547200

Cited by 12 publications

(17 citation statements)

References 33 publications

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“…For example, DLP is the homolog of Daxx, a known transcriptional and cell signaling regulator and regulator of mammalian p53 (Gostissa et al 2004;Zhao et al 2004). DLP binds to the carboxyl terminus of Dmp53 and can act to repress Dmp53 mediated responses (Bodai et al 2007), however, it is not clear whether it does so by regulating Dmp53 transcription or through some other mechanism.…”

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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“…Targeted deletion of Daxx alleles results in embryonic lethality in mouse, 4 although loss of DLP expression does not appear to affect viability in D. melanogaster. 21 In mammals, the Daxx locus resides near the MHC complex locus and this synteny is preserved from mouse to humans. 51 This genetic linkage promoted speculation that Daxx might have a role in immune responses.…”

Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

“…Notably, two putative coiled-coil sequences are present in the Daxx core domain and as such they probably play structural roles; for example, the core domain may mediate homo or hetero-oligomerization via the coiledcoil sequences. Interestingly, like human Daxx that physically binds tumor suppressor p53 and regulates its activity, 10,20 interaction between DLP and Drosophila p53 is also observed, 21 suggesting that the Daxx family of proteins probably also have conserved functions. Nonetheless, it remains to be determined whether the conserved functions of Daxx family are mediated through common functional domains.…”

Section: Introductionmentioning

confidence: 99%

Identification of two independent SUMO-interacting motifs in Daxx: Evolutionary conservation from Drosophila to humans and their biochemical functions

Santiago¹,

Godsey²,

Hossain³

et al. 2009

Cell Cycle

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Daxx is essential for embryonic development and implicated in apoptosis and transcriptional regulation. It is found only in the animal kingdom and appears to arise first in insects. In the Drosophila genus, the Daxx orthologs are much larger than those in other species. Here we show that in addition to a conserved core of ~200 residues, Daxx possesses several conserved domains and two essentially invariable short SUMO-interacting motifs (SIMs), each located at one or the other terminus of the protein.

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“…The Drosophila homolog of Daxx, referred to as DLP, has been described very recently (44): it encodes a large peptide with similarity to Daxx in the C terminus. We observed that DLP accumulates in nuclear dots when overexpressed in Drosophila S2 cells, and these dots co-localize with GFP-dSUMO and human PML IV (supplemental Fig.…”

Section: Sumoylation Affects P53 Localization To Nuclear Dots Definedmentioning

confidence: 99%

Modification of Drosophila p53 by SUMO Modulates Its Transactivation and Pro-apoptotic Functions

Mauri

McNamee

Lunardi

et al. 2008

Journal of Biological Chemistry

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Conjugation to SUMO is a reversible post-translational modification that regulates several transcription factors involved in cell proliferation, differentiation, and disease. The p53 tumor suppressor can be modified by SUMO-1 in mammalian cells, but the functional consequences of this modification are unclear. Here, we demonstrate that the Drosophila homolog of human p53 can be efficiently sumoylated in insect cells. We identify two lysine residues involved in SUMO attachment, one at the C terminus, between the DNA binding and oligomerization domains, and one at the N terminus of the protein. We find that sumoylation helps recruit Drosophila p53 to nuclear dot-like structures that can be marked by human PML and the Drosophila homologue of Daxx. We demonstrate that mutation of both sumoylation sites dramatically reduces the transcriptional activity of p53 and its ability to induce apoptosis in transgenic flies, providing in vivo evidence that sumoylation is critical for Drosophila p53 function.

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Daxx-like Protein of Drosophila Interacts with Dmp53 and Affects Longevity and Ark mRNA Level

Cited by 12 publications

References 33 publications

Phylogeny and Function of the Invertebrate p53 Superfamily

Phylogeny and Function of the Invertebrate p53 Superfamily

Identification of two independent SUMO-interacting motifs in Daxx: Evolutionary conservation from Drosophila to humans and their biochemical functions

Modification of Drosophila p53 by SUMO Modulates Its Transactivation and Pro-apoptotic Functions

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