Ubiquitin and the enigma of intracellular protein degradation

Jennissen, H. P.

doi:10.1007/978-3-642-85252-7_14

Cited by 5 publications

(9 citation statements)

References 294 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ca 2+ -dependent uCaM-synthetase has previously been detected in most tissues of the rabbit and also in yeast (Saccharomyces cerevisiae). 4 As shown here, in human tissue uCaM-synthetase is detectable as well. Compared 486 Majetschak, Suciu, Häsler, Obertacke, Schade, Jennissen with the previously described enzyme activities in cytosolic lysates from various rabbit tissues, 12 human PBMNC lysates were found to contain the highest specific uCaM-synthetase activities.…”

Section: Discussionsupporting

confidence: 73%

“…Ubiquitin has been shown to be involved in cell differentiation, heat shock response, antigen presentation and regulation of protein breakdown by the ubiquitin-proteasomepathway. [2][3][4][5] Moreover, the ubiquitin-proteasome pathway is regarded as playing a crucial role in inflammation and sepsis as well as in regulation of inflammatory cell responses, e.g. in regulation of the transcriptional factor, NF-κB, which controls for example TNF-α production.…”

Section: Introductionmentioning

confidence: 99%

“…The latter has been shown to consist of two different components (uCaM-Syn F1 and F2) and is specific for Ca 2+ -calmodulin, whereas the ubiquitin protein ligase is a three component system (E1-E3) which typically catalyzes the ubiquitylation according to the N-end rule. 4 Because as yet neither the ubiquitylation rate of cytosolic proteins, as a result of the total ubiquitin-protein ligase activity, nor the specific ubiquitylation of calmodulin has been determined in human mononuclear cells, we studied these cytosolic protein ubiquitylation systems in normal and in endotoxin-stimulated human peripheral blood mononuclear cells (PBMNCs).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cytosolic protein ubiquitylation in normal and endotoxin stimulated human peripheral blood mononuclear cells

Majetschak

Suciu

Hasler

et al. 2000

Journal of Endotoxin Research

Self Cite

View full text Add to dashboard Cite

The ubiquitin-proteasome pathway is regarded as playing a crucial role in protein breakdown in inflammation and sepsis as well as in the regulation of inflammatory cell responses. In this pathway, ubiquitylation of target proteins is believed to act as a recognition signal for degradation by the 26S proteasome. As yet neither the ubiquitylation rate of cytosolic proteins, as a result of the total ubiquitin-protein ligase (tUbPL) activity, nor the specific ubiquitylation of calmodulin (ubiquitin-calmodulin ligase, uCaM-synthetase) has been determined in human mononuclear cells. Therefore, we studied cytosolic protein ubiquitylation in normal and in endotoxin (LPS)-stimulated human peripheral blood mononuclear cells (PBMNCs).PBMNCs from healthy volunteers were incubated with 0 or 100 ng/ml LPS for 18 h. Cytosolic extracts were obtained by hypotonic lysis and ultracentrifugation. TUbPL was measured as [(125)I]-[CT]-ubiquitin incorporation into the sum of cytosolic proteins. UCaM-synthetase activity was quantified with the fluphenazine (FP)-Sepharose affinity adsorption test. Endotoxin stimulation appears to inhibit tUbPL 3.7 +/- 2.7-fold to 48 +/- 43 fkat/mg (n = 6). UCaM-synthetase in cultures (n = 5) without endotoxin was determined to be 91 +/- 32 fkat/mg +Ca(2+) and 29 +/- 23 fkat/mg -Ca(2+). With endotoxin uCaM-synthetase was 138 +/- 73 fkat/mg +Ca(2+) and 14 +/- 22 fkat/mg -Ca(2+). Ca(2+)-specificity (ratio +/- Ca(2+)) of uCaM-synthetase increases from 3.1 without LPS to 10 after LPS stimulation, which was caused by a 2-fold decrease in minus Ca(2+) activity and a 1.5-fold increase in plus Ca(2+) activity. The data indicate specific regulatory effects of endotoxin on the cytosolic ubiquitylation systems in human PBMNCs.

show abstract

Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cytosolic protein ubiquitylation in normal and endotoxin stimulated human peripheral blood mononuclear cells

Majetschak

Suciu

Hasler

et al. 2000

Journal of Endotoxin Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Both elastic fibres and fibrillar collagens are uniquely long-lived (Sivan et al 2008;Shapiro et al 1991) compared to intracellular proteins (Jennissen 1995). The low turnover rate of these structural ECM proteins exposes them to degradation by a range of processes; enzymatic, chemical or biophysical.…”

Section: Introductionmentioning

confidence: 99%

Cross-linking of structural proteins in ageing skin: an in situ assay for the detection of amine oxidase activity

et al. 2012

View full text Add to dashboard Cite

With increasing age, dynamic tissues such as lungs, blood vessels and skin lose their ability to both deform and recoil, culminating in tissue stiffening. This loss of tissue elasticity, which profoundly impacts tissue function and thus morbidity, may be due not only to changes in the relative abundance of key extracellular matrix proteins within tissues but also to their accumulation of post-translational modifications. Whilst to date attention has focussed primarily on the age-related non-enzymatic formation of advanced glycation end products, the accumulation of pathological enzyme-mediated cross-links may also lead to age-related tissue stiffening. The lysyl oxidase (LOX) family of enzymes are constitutively expressed in adult tissues and are known to drive the catalysis of cross-links in both fibrillar collagens and elastin. Although immunochemical approaches are commonly used to localise the inactive pro-enzyme of LOX, and biochemical methods are employed to quantify activity in homogenised tissue, they do not allow for the in situ localisation of the enzyme. Thus, we have developed a novel assay to both detect and localise LOX enzyme activity in situ. LOX family members are amine oxidases and this assay uses the principle that an amine substrate in the presence of this class of enzyme will be oxidised to an aldehyde and hydrogen peroxide (H2O2). In turn, H2O2, when combined with luminol and horseradish peroxidase, will produce a light-emitting reaction that can be detected by film autoradiography. The development of a technique to localise specific amine oxidase activity in tissue sections may provide crucial additional information on the exact role played by this class of enzymes in mediating age-related tissue stiffening.

show abstract

“…The Ub-proteasome proteolytic apparatus plays an important role in cell cycle progression, since it selectively degrades nuclear oncoproteins such as cyclins, c-fos, cmyc, p53 [5,7,16]. Moreover, several cell surface receptors were shown to be ubiquitinated, suggesting that Ub-proteasome proteolytic system could be involved in their turnover [6,31].…”

Section: Introductionmentioning

confidence: 99%

Ubiquitin Cytochemical Changes During Azaserine-Initiated Pancreatic Carcinogenesis

Tóth

Vastagh

Pálfia

et al. 2001

Acta Biologica Hungarica

View full text Add to dashboard Cite

The ubiquitin (Ub)-proteasome proteolytic system is highly selective, and the specific proteins involved in cell division, growth, activation, signaling and transcription are degraded at different rate depending on the physio-pathological state of the cell. Ubiquitination serves first of all as a signal for protein degradation of short-lived and abnormal proteins under several stressful conditions. The immunocytochemical localization of Ub in some malignant tumours has recently been presented and differences in Ub expression has been observed during malignant transformation. Change in the level of Ub and Ub-conjugated proteins might reflect a higher metabolic-catabolic ratio in neoplastic cells. Most studies have been focused on the malignant stage of tumour progression, and only a few papers have dealt with the change in Ub and Ub-protein conjugates level during the whole progression. To address this problem, we applied an azaserine-induced pancreatic carcinogenesis model, in which premalignant and malignant stages were investigated throughout the progression. The level of Ub immunoreactivity was measured in nucleus and cytoplasm by electron microscopic immunocytochemical and morphometrical methods. We found a significant increase of Ub level in the nucleus and the cytoplasmic area in premalignant atypical acinar cell nodule (AACN) cells and in malignant adenocarcinoma in situ (CIS) cells at month 20 after initiation.

show abstract

Ubiquitin and the enigma of intracellular protein degradation

Cited by 5 publications

References 294 publications

Cytosolic protein ubiquitylation in normal and endotoxin stimulated human peripheral blood mononuclear cells

Cytosolic protein ubiquitylation in normal and endotoxin stimulated human peripheral blood mononuclear cells

Cross-linking of structural proteins in ageing skin: an in situ assay for the detection of amine oxidase activity

Ubiquitin Cytochemical Changes During Azaserine-Initiated Pancreatic Carcinogenesis

Contact Info

Product

Resources

About