PARP-1 modifies the effectiveness of p53-mediated DNA damage response

Valenzuela, Marı́a Teresa; Guerrero, R.; Núñez, María Isabel; Almodóvar, José Mariano Ruiz de; Sarker, Malabika; Murcia, Gilbert de; Oliver, F. Javier

doi:10.1038/sj.onc.1205169

Cited by 111 publications

(76 citation statements)

References 35 publications

(30 reference statements)

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“…The remaining chromatin-associated interactions identified by in-solution digestion will be described in a separate publication. This link is notable in light of previous findings that FKBP25 regulates p53 levels via MDM2 (Ochocka et al 2009), and KAP1, PARP1, and RPA1 all have links to the regulation of p53 in DNA damage (Valenzuela et al 2002;Bochkareva et al 2005;Wang et al 2005). In support of a potential role for FKBP25 in chromatin biology, histone deacetylaces (HDAC) 1 and 2 have been identified as FKBP25-associated proteins (Yang et al 2001), and Mybbp1a and KAP1 are found in complexes containing HDAC1 and 2 (Schultz et al 2001;Tan et al 2012).…”

Section: Fkbp25 Localizes To the Nucleus And Nucleolus And Associatesmentioning

confidence: 90%

The prolyl isomerase, FKBP25, interacts with RNA-engaged nucleolin and the pre-60S ribosomal subunit

Gudavicius

Dilworth

Serpa

et al. 2014

RNA

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Peptidyl-proline isomerases of the FK506-binding protein (FKBP) family belong to a class of enzymes that catalyze the cis-trans isomerization of prolyl-peptide bonds in proteins. A handful of FKBPs are found in the nucleus, implying that the isomerization of proline in nuclear proteins is enzymatically controlled. FKBP25 is a nuclear protein that has been shown to associate with chromatin modifiers and transcription factors. In this study, we performed the first proteomic characterization of FKBP25 and found that it interacts with numerous ribosomal proteins, ribosomal processing factors, and a small selection of chromatin modifiers. In agreement with previous reports, we found that nucleolin is a major FKBP25-interacting protein and demonstrated that this interaction is dependent on rRNA. FKBP25 interacts with the immature large ribosomal subunit in nuclear extract but does not associate with mature ribosomes, implicating this FKBP's action in ribosome biogenesis. Despite engaging nascent 60S ribosomes, FKBP25 does not affect steady-state levels of rRNAs or its pre-rRNA intermediates. We conclude that FKBP25 is likely recruited to preribosomes to chaperone one of the protein components of the ribosome large subunit.

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Section: Fkbp25 Localizes To the Nucleus And Nucleolus And Associatesmentioning

confidence: 90%

The prolyl isomerase, FKBP25, interacts with RNA-engaged nucleolin and the pre-60S ribosomal subunit

Gudavicius

Dilworth

Serpa

et al. 2014

RNA

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“…For instance, several studies using either PARP inhibitors or PARP knockout (KO) mice demonstrate the important role of this protein in maintaining DNA integrity, 12 and several benzamide-derived PARP inhibitors are being tested to treat cancer patients. 13,14 One of the targets of PARP-1 is p53, [15][16][17][18] promoting its poly(ADPribosyl)ation and accumulation in the nucleus, to control its transcriptional activity. However, hyperactivation of PARP-1 after severe DNA damage can cause NAD and ATP depletion leading to a unique form of necrotic cell death named parthanatos.…”

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confidence: 99%

“…13,14 One of the targets of PARP-1 is p53, [15][16][17][18] promoting its poly(ADPribosyl)ation and accumulation in the nucleus, to control its transcriptional activity. However, hyperactivation of PARP-1 after severe DNA damage can cause NAD and ATP depletion leading to a unique form of necrotic cell death named parthanatos.…”

mentioning

confidence: 99%

p53 regulates a non-apoptotic death induced by ROS

et al. 2013

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DNA damage induced by reactive oxygen species and several chemotherapeutic agents promotes both p53 and poly (ADP-ribose) polymerase (PARP) activation. p53 activation is well known to regulate apoptotic cell death, whereas robust activation of PARP-1 has been shown to promote a necrotic cell death associated with energetic collapse. Here we identify a novel role for p53 in modulating PARP enzymatic activity to regulate necrotic cell death. In mouse embryonic fibroblasts, human colorectal and human breast cancer cell lines, loss of p53 function promotes resistance to necrotic, PARP-mediated cell death. We therefore demonstrate that p53 can regulate both necrotic and apoptotic cell death, mutations or deletions in this tumorsuppressor protein may be selected by cancer cells to provide not only their resistance to apoptosis but also to necrosis, and explain resistance to chemotherapy and radiation even when it kills via non-apoptotic mechanisms. Cell Death and Differentiation (2013) 20, 1465-1474 doi:10.1038/cdd.2013 published online 24 May 2013 Mutations in the p53 protein (encoded by TP53 in humans) are detected in approximately half of human cancers.1-3 This tumor-suppressor protein regulates apoptosis, cell cycle and metabolism. Numerous signaling pathways converge in p53 after cellular insults, including DNA damage, oncogene activation or hypoxia. For instance, after DNA injury, p53 is activated promoting cell cycle arrest, transactivation of repairing enzymes and, if the damage cannot be repaired, apoptosis.4 Under these conditions, p53 is posttranscriptionally modified, assisting in the expression of several proteins including p21, GADD45/PCNA or pro-apoptotic genes like BAX, PUMA, NOXA, BID and APAF-1.5 Moreover, a directly pro-apoptotic cytosolic function has been described, directly binding to anti-apoptotic proteins (BCL-2 and BCL-XL) and directly activating BAX and BAK to induce mitochondrial outer membrane permeabilization (MOMP) and apoptosis in a transcriptional-independent manner. 6 Because of its broad effects in the cell, loss of p53 activity confers growth advantage and ensures survival in cancer cells by inhibiting the apoptotic response necessary for tumor suppression. [7][8][9] Following DNA damage, poly(ADP-ribose)polymerase-1 (PARP-1), the founding member of the PARP superfamily of proteins, is activated by DNA nicks and rapidly uses nicotinamide adenine dinucleotide (NAD) to polymerize adenosine diphosphate (ADP)-ribose and covalently modify target proteins to orchestrate DNA repair. These include chromatin structure regulators and DNA modulators like histones, HMG proteins, topoisomerases I and II, DNA helicases, single-strand break repair and base-excision repair enzymes, and different transcription factors.10,11 Briefly, PARP activation promotes chromatin relaxation and the recruitment of base-excision repair proteins, including XRCC1, DNA ligase III and DNA polimerase b, that will ensure the DNA repair. For instance, several studies using either PARP inhibitors or PARP knockout (KO) ...

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“…PARP-1 is an abundant nuclear enzyme that binds to DNA single-strand breaks. This binding triggers its catalytic activity, the synthesis of ADP-ribose polymers, and their attachment to acceptor proteins including itself (7,8,(22)(23)(24)(25), thereby initiating such events as recruitment of DNA repair proteins (7,8,(26)(27)(28) and modulation of p53-and NF-B-dependent signaling pathways (29)(30)(31)(32)(33) or chromatin structure (34).…”

mentioning

confidence: 99%

Regulation of poly(ADP-ribose) polymerase 1 activity by the phosphorylation state of the nuclear NAD biosynthetic enzyme NMN adenylyl transferase 1

Berger

Lau

Ziegler

2007

Proc. Natl. Acad. Sci. U.S.A.

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Nuclear NAD ؉ metabolism constitutes a major component of signaling pathways. It includes NAD ؉ -dependent protein deacetylation by members of the Sir2 family and protein modification by poly(ADP-ribose) polymerase 1 (PARP-1). PARP-1 has emerged as an important mediator of processes involving DNA rearrangements. High-affinity binding to breaks in DNA activates PARP-1, which attaches poly(ADP-ribose) (PAR) to target proteins. NMN adenylyl transferases (NMNATs) catalyze the final step of NAD ؉ biosynthesis. We report here that the nuclear isoform NMNAT-1 stimulates PARP-1 activity and binds to PAR. Its overexpression in HeLa cells promotes the relocation of apoptosis-inducing factor from the mitochondria to the nucleus, a process known to depend on poly(ADP-ribosyl)ation. Moreover, NMNAT-1 is subject to phosphorylation by protein kinase C, resulting in reduced binding to PAR. Mimicking phosphorylation, substitution of the target serine residue by aspartate precludes PAR binding and stimulation of PARP-1. We conclude that, depending on its state of phosphorylation, NMNAT-1 binds to activated, automodifying PARP-1 and thereby amplifies poly(ADP-ribosyl)ation.apoptosis ͉ NAD biosynthesis ͉ poly(ADP-ribosyl)ation ͉ protein phosphorylation N MN adenylyl transferase (NMNAT) is an essential enzyme because it catalyzes the final step of NAD ϩ biosynthesis (1). There are three isoforms in humans that exhibit tissue-and organelle-specific expression (2). Because the biological role of NAD ϩ and NADH (collectively termed NAD) has long been thought to be confined to their function as electron carriers, the nuclear localization of the major isoforms, human NMNAT-1 (3) and yeast Nma2 (4), was somewhat puzzling. However, recent research has revealed many important regulatory functions of the pyridine nucleotides, some of which take place within the nucleus (5).NAD ϩ serves as substrate for covalent protein modifications such as mono(ADP-ribosyl)ation (6), poly(ADP-ribosyl)ation (7,8), and protein deacetylation by sirtuins, proteins of the silent information regulator 2 (Sir2) family (9). Pyridine nucleotides are also direct precursors of two calcium-mobilizing messengers, cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate (NAADP ϩ ) (10 -13). The predominant NAD ϩ -consuming activity, poly(ADP-ribosyl)ation by poly(ADPribose) polymerase 1 (PARP-1), occurs within the nucleus, as does NAD ϩ -dependent protein deacetylation by sirtuins. Consequently, substrate supply by NMNAT-1 may directly influence these processes. Overexpression of NMNAT-1 extends the lifespan of eukaryotic cells, which has been attributed to augmented NAD ϩ -dependent histone deacetylation catalyzed by Sir2p or its homologs (4,(14)(15)(16)(17)(18). Increased NMNAT activity is also required for the axon-sparing activity of the chimeric slow Wallerian degeneration (Wld s ) protein, which is composed of 19 amino acids of the ubiquitin assembly protein Ufd2a and full-length NMNAT-1 (19).Although suggested previously (3, 20, 21), a functional intera...

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PARP-1 modifies the effectiveness of p53-mediated DNA damage response

Cited by 111 publications

References 35 publications

The prolyl isomerase, FKBP25, interacts with RNA-engaged nucleolin and the pre-60S ribosomal subunit

The prolyl isomerase, FKBP25, interacts with RNA-engaged nucleolin and the pre-60S ribosomal subunit

p53 regulates a non-apoptotic death induced by ROS

Regulation of poly(ADP-ribose) polymerase 1 activity by the phosphorylation state of the nuclear NAD biosynthetic enzyme NMN adenylyl transferase 1

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