Proteomic screen reveals Fbw7 as a modulator of the NF-κB pathway

Arabi, Azadeh; Ullah, Karim; Branca, Rui M.; Johansson, Johan R.; Bandarra, Daniel; Haneklaus, Moritz; Fu, Jingzhu; Ariës, Ingrid M.; Nilsson, Peter; Boer, Monique L. den; Pokrovskaja, Katja; Grandér, Dan; Xiao, Gutian; Rocha, Sónia; Lehtiö, Janne; Sangfelt, Olle

doi:10.1038/ncomms1975

Cited by 84 publications

(76 citation statements)

References 46 publications

(70 reference statements)

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“…SCF Fbw7 has been shown to target a number of important cellular regulatory proteins for ubiquitylation and proteasomal degradation. These include, among others, cyclins E1 (31)(32)(33) and E2 (34), c-myc (35)(36)(37), c-Jun, SREBP (38), PGC1-␣ (39), Notch (40,41), myeloid cell leukemia 1 (Mcl-1) (42,43), and NF-B2 (44)(45)(46). Since several of these proteins are oncoproteins, it is not surprising that Fbw7 has been found to be mutated in a broad spectrum of human cancers and is therefore considered a tumor suppressor (47,48).…”

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confidence: 99%

Parkin-Dependent Degradation of the F-Box Protein Fbw7β Promotes Neuronal Survival in Response to Oxidative Stress by Stabilizing Mcl-1

Ekholm-Reed

Goldberg

Schlossmacher

et al. 2013

Molecular and Cellular Biology

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confidence: 99%

Parkin-Dependent Degradation of the F-Box Protein Fbw7β Promotes Neuronal Survival in Response to Oxidative Stress by Stabilizing Mcl-1

Ekholm-Reed

Goldberg

Schlossmacher

et al. 2013

Molecular and Cellular Biology

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“…Recent developments in methods and instruments for mass spectrometry enable quantitative proteomics analysis of complex samples with good coverage (1)(2)(3)(4). Several techniques for quantification by mass spectrometry exist, both using isotopic labeling and label free methods (5,6).…”

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confidence: 99%

Defining, Comparing, and Improving iTRAQ Quantification in Mass Spectrometry Proteomics Data

Hultin‐Rosenberg

Forshed

Branca

et al. 2013

Molecular & Cellular Proteomics

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The purpose of this study was to generate a basis for the decision of what protein quantities are reliable and find a way for accurate and precise protein quantification. To investigate this we have used thousands of peptide measurements to estimate variance and bias for quantification by iTRAQ (isobaric tags for relative and absolute quantification) mass spectrometry in complex human samples. A549 cell lysate was mixed in the proportions 2:2:1:1:2:2:1:1, fractionated by high resolution isoelectric focusing and liquid chromatography and analyzed by three mass spectrometry platforms; LTQ Orbitrap Velos, 4800 MALDI-TOF/TOF and 6530 Q-TOF. We have investigated how variance and bias in the iTRAQ reporter ions data are affected by common experimental variables such as sample amount, sample fractionation, fragmentation energy, and instrument platform. Based on this, we have suggested a concept for experimental design and a methodology for protein quantification. By using duplicate samples in each run, each experiment is validated based on its internal experimental variation. The duplicates are used for calculating peptide weights, unique to the experiment, which is used in the protein quantification. By weighting the peptides depending on reporter ion intensity, we can decrease the relative error in quantification at the protein level and assign a total weight to each protein that reflects the protein quantitation confidence. We also demonstrate the usability of this methodology in a cancer cell line experiment as well as in a clinical data set of lung cancer tissue samples. In conclusion, we have in this study developed a methodology for improved protein quantification in shotgun proteomics and introduced a way to assess quantification for proteins with few peptides. The experimental design and developed algorithms decreased the relative protein quantification error in the analysis of complex biological samples. Recent developments in methods and instruments for mass spectrometry enable quantitative proteomics analysis of complex samples with good coverage (1-4). Several techniques for quantification by mass spectrometry exist, both using isotopic labeling and label free methods (5, 6). Quantification by isotopic labeling can be done on precursor ion level or by quantifying isobaric label fragments in fragment spectra. Isotope-coded affinity tag (7), isobaric tags for relative and absolute quantification (iTRAQ) 1 (8), and stable isotope labeling by amino acids in cell culture (SILAC) (9) are among the most commonly used labeling methods based on stable isotopes. iTRAQ allows for simultaneous relative quantification of up to eight samples within a single run. Quantification by mass spectrometry is however a challenge, and several factors contribute to the uncertainty in the quantitative estimate; differences in labeling efficiency, protein digestion, precursor mixing, ion suppression, peak detection, data preprocessing, and data analysis (10). The quality of quantitation methods can be measured in terms of precision ...

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“…Our own work, in collaboration with Sangfelt's laboratory, has shown that FBW7 interacts directly with p100 via a conserved degron and that it promotes degradation of p100 through the GSK3β in phosphorylation-dependent manner. This interaction also affects the complex between the active form of p100, p52, and RelB, which consequently changes the apoptotic balance in the cell 30 . However, what is the contribution of FBW7-mediated regulation of NF-κB towards the regulation of HIF-1α is not yet known.…”

Section: Hif and Nf-κb Functional Crosstalk Shared Targets And Activmentioning

confidence: 99%

A tale of two transcription factors: NF-kB and HIF crosstalk

Bandarra¹,

Rocha²

2013

OA Molecular and Cell Biology

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Introduction Hypoxia-inducible factor is a key transcriptional factor involved in the cellular response to low levels of oxygen, hypoxia. Moreover, hypoxiainducible factor has been recently associated with a role in inflammation and immunity. Importantly, hypoxiainducible factor is regulated by the major inflammatory responsive transcription factor, nuclear factor-κB. These two major pathways have been intimately linked. On one hand, they share a number of common target genes; on the other hand, physical interactions between hypoxiainducible factor subunits and nuclear factor-κB have been observed. Even though the role of nuclear factor-κB over hypoxia-inducible factor is fairly well-known, the involvement of hypoxia-inducible factor over the nuclear factor-κB pathway is not. Given the overlap between these pathways, it would not be surprising to find a functional involvement of hypoxiainducible factor in processes where nuclear factor-κB is involved. In this review, we will describe the communalities between hypoxia-inducible factor and nuclear factor-κB pathways, highlighting the crosstalk that occurs in a variety of conditions. Conclusion Taken together all the communalities between hypoxia-inducible factor and nuclear factor-κB pathways, there is no doubt that a cross-

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Proteomic screen reveals Fbw7 as a modulator of the NF-κB pathway

Cited by 84 publications

References 46 publications

Parkin-Dependent Degradation of the F-Box Protein Fbw7β Promotes Neuronal Survival in Response to Oxidative Stress by Stabilizing Mcl-1

Parkin-Dependent Degradation of the F-Box Protein Fbw7β Promotes Neuronal Survival in Response to Oxidative Stress by Stabilizing Mcl-1

Defining, Comparing, and Improving iTRAQ Quantification in Mass Spectrometry Proteomics Data

A tale of two transcription factors: NF-kB and HIF crosstalk

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