Identification of polyubiquitin binding proteins involved in NF-κB signaling using protein arrays

Fenner, Beau J.; Scannell, Michael; Prehn, Jochen H.M.

doi:10.1016/j.bbapap.2009.02.013

Cited by 58 publications

(75 citation statements)

References 46 publications

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“…4,5 However, intracellular targets for ZNF313 have not been identified yet. We observed that ZNF313 destabilizes p21 WAF1 , p27 KIP1 and p57 KIP2 but not the INK4 family members of the CDK inhibitors, and this effect is abolished by a mutation of the RING domain, confirming that the RING domain is critical for its E3 ligase function.…”

Section: Discussionmentioning

confidence: 99%

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ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21WAF1

Han

et al. 2013

Cell Death Differ

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ZNF313 encoding a zinc-binding protein is located at chromosome 20q13.13, which exhibits a frequent genomic amplification in multiple human cancers. However, the biological function of ZNF313 remains largely undefined. Here we report that ZNF313 is an ubiquitin E3 ligase that has a critical role in the regulation of cell cycle progression, differentiation and senescence. In this study, ZNF313 is initially identified as a XIAP-associated factor 1 (XAF1)-interacting protein, which upregulates the stability and proapoptotic effect of XAF1. Intriguingly, we found that ZNF313 activates cell cycle progression and suppresses cellular senescence through the RING domain-mediated degradation of p21 WAF1 . ZNF313 ubiquitinates p21 WAF1 and also destabilizes p27 KIP1 and p57 KIP2 , three members of the CDK-interacting protein (CIP)/kinase inhibitor protein (KIP) family of cyclin-dependent kinase inhibitors, whereas it does not affect the stability of the inhibitor of CDK (INK4) family members, such as p16INK4A and p15 INK4B . ZNF313 expression is tightly controlled during the cell cycle and its elevation at the late G1 phase is crucial for the G1-to-S phase transition. ZNF313 is induced by mitogenic growth factors and its blockade profoundly delays cell cycle progression and accelerates p21 WAF1 -mediated senescence. Both replicative and stress-induced senescence are accompanied with ZNF313 reduction. ZNF313 is downregulated during cellular differentiation process in vitro and in vivo, while it is commonly upregulated in many types of cancer cells. ZNF313 shows both the nuclear and cytoplasmic localization in epithelial cells of normal tissues, but exhibits an intense cytoplasmic distribution in carcinoma cells of tumor tissues. Collectively, ZNF313 is a novel E3 ligase for p21 WAF1 , whose alteration might be implicated in the pathogenesis of several human diseases, including cancers.

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Section: Discussionmentioning

confidence: 99%

“…4,5 The ZNF313 gene is located at human chromosome 20q13.13, which displays a frequent genomic amplification in many types of malignancies, including cervical, gastric and colon cancer. 3,6,7 Moreover, the ZNF313 gene was identified to be amplified and its expression level is elevated in patients with psoriasis, an immune-mediated skin disease.…”

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confidence: 99%

ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21WAF1

Han

et al. 2013

Cell Death Differ

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“…Transfection efficiencies ranged typically between 5 and 20%, while triplevector co-transfection efficiencies were determined using visibly-expressed fluorescent protein at 6863.84% (n55 wells). The following transfection vectors were used: pCMV6-Entry-Myc-FLAG-FHF1b (PCR-amplified and subcloned into pCMV6-Entry from a human cDNA clone; NM_004113.3, Origene), pcDNA4/HisMaxA-NEMO (Fenner et al, 2009), p65-EGFP-N1 (a generous gift of E. Floettmann and M. Rowe, Cardiff, UK), EGFP-N1 (Clontech, Heidelberg, Germany) served to determine positively-transfected cells or as control, EB1-GFP (Piehl and Cassimeris, 2003), wild-type and K44M-IKKb [kinase-dead, Addgene plasmids 11103 and 11104 (Mercurio et al, 1997)], wildtype and NEMO-L329P [Addgene plasmids 11970 and 11971 (Wu et al, 2006)] were used. Two-hybrid complementation plasmids were generated by ligation into the according vectors as directed by the manufacturer's protocol (CheckMateH, Promega, Southampton, UK).…”

Section: Transfection Of Primary Neuronsmentioning

confidence: 99%

Fibroblast growth factor homologous factor 1 interacts with NEMO to regulate NF-κB signaling in neurons

König

Fenner

Byrne

et al. 2012

Journal of Cell Science

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SummaryNeuronal survival and plasticity critically depend on constitutive activity of the transcription factor nuclear factor-kB (NF-kB). We here describe a role for a small intracellular fibroblast growth factor homologue, the fibroblast growth factor homologous factor 1 (FHF1/ FGF12), in the regulation of NF-kB activity in mature neurons. FHFs have previously been described to control neuronal excitability, and mutations in FHF isoforms give rise to a form of progressive spinocerebellar ataxia. Using a protein-array approach, we identified FHF1b as a novel interactor of the canonical NF-kB modulator IKKc/NEMO. Co-immunoprecipitation, pull-down and GAL4-reporter experiments, as well as proximity ligation assays, confirmed the interaction of FHF1 and NEMO and demonstrated that a major site of interaction occurred within the axon initial segment. Fhf1 gene silencing strongly activated neuronal NF-kB activity and increased neurite lengths, branching patterns and spine counts in mature cortical neurons. The effects of FHF1 on neuronal NF-kB activity and morphology required the presence of NEMO. Our results imply that FHF1 negatively regulates the constitutive NF-kB activity in neurons.

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“…The ubiquitinase UBC and Ubiquitin Carboxyl-terminal Hydrolase isozyme L1 (UCHL1) are downregulated in aged blastocysts, as well as proteins containing a RING finger domain that plays a key role in the ubiquitination pathway during embryonic development [37,38] such as RING Finger protein 223 (RNF223) and Kelch-like protein 17 (KLHL17). Instead, the expression of the 26S Proteasome non-ATPase regulatory subunit 4 (PSMD4), a component of the 26S proteasome complex responsible for ubiquitylated proteins degradation, and the AN1-type zinc finger protein 6 (ZFAND6), a polyubiquitin binding protein involved in regulating NFkappaB signaling [39], are completely switched off. Interestingly, several differential expressed proteins are substrate of Small Ubiquitin MOdifier (SUMO), which is also involved in regulating embryonic viability in mammals [40].…”

Section: Discussionmentioning

confidence: 99%

“…All consenting patients undergoing fertility treatment at the Humanitas Fertility Center, Humanitas Research Hospital, Rozzano, Italy, with supernumerary blastocysts were included in the study irrespective of the woman's age (range years [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41], infertility diagnosis (female or male), ovarian stimulation protocol (use of GnRH agonist or antagonist protocols in combination with recombinant and/or highly purified urinary gonadotropins), or performance of standard IVF or intracytoplasmic sperm injection (ICSI). The study was part of a trial on blastocoel fluid collection in order to test the safety of this procedure on pregnancy outcome [22].…”

Section: Patient Populationmentioning

confidence: 99%

Proteomic profile of maternal-aged blastocoel fluid suggests a novel role for ubiquitin system in blastocyst quality

Tedeschi

Albani

Borroni

et al. 2016

J Assist Reprod Genet

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Purpose The etiology of maternal aging, a common cause of female factor infertility and a rate-limiting step in vitro fertilization (IVF) success, remains still unclear. Proteomic changes responsible for the impaired successful pregnancy outcome after IVF with aged blastocysts have not been yet evaluated. The objective of this prospective study was to employ proteomic techniques and bioinformatic tools to enlight differences at the protein level in blastocoel fluid of aged and younger woman. Methods Protein composition of human blastocoel fluid isolated by micromanipulation from 46 blastocysts of women aged <37 years (group A) and 29 of women aged ≥37 years (group B) have been identified by a shotgun proteomic approach based on high-resolution nano-liquid chromatography electrospray-ionization-tandem mass spectrometry (nLC-ESI-MS/MS) using label free for the relative quantification of their expression levels. Results The proteomic analysis leads to the identification and quantification of 148 proteins; 132 and 116 proteins were identified in groups A and B, respectively. Interestingly, the identified proteins are mainly involved in processes aimed at fine tuning embryo implantation and development. Among the 100 proteins commonly expressed in both groups, 17 proteins are upregulated and 44 downregulated in group B compared to group A. Overall, the analysis identified 33 proteins, which were increased or present only in B while 76 were decreased in B or present only in A. Conclusions Data revealed that maternal aging mainly affects blastocyst survival and implantation through unbalancing the equilibrium of the ubiquitin system known to play a crucial role in fine-tuning several aspects required to ensure successful pregnancy outcome.

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Identification of polyubiquitin binding proteins involved in NF-κB signaling using protein arrays

Cited by 58 publications

References 46 publications

ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21WAF1

ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21WAF1

Fibroblast growth factor homologous factor 1 interacts with NEMO to regulate NF-κB signaling in neurons

Proteomic profile of maternal-aged blastocoel fluid suggests a novel role for ubiquitin system in blastocyst quality

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