Expression of proteasomal proteins in ten different tumor cell lines

Afjehi‐Sadat, Leila; Gruber-Olipitz, Mariella; Felizardo, Maureen; Slavc, Irene; Lubec, Gert

doi:10.1007/s00726-004-0125-1

Cited by 19 publications

(15 citation statements)

References 30 publications

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“…For example, POH1 expression was increased up to 23.7-fold in the sponge Geodia cydonium after exposure to toxins under controlled conditions or in naturally contaminated waters (32). POH1 was also shown to be elevated in cancer cells, notably ovarian carcinomas, melanomas, and leukemic cells (33), where it can be used as a marker for malignancy. It will be of interest to determine how such fluctuations in POH1 influence c-Jun stability and activity in these systems.…”

Section: Discussionmentioning

confidence: 99%

The 19 S Proteasomal Subunit POH1 Contributes to the Regulation of c-Jun Ubiquitination, Stability, and Subcellular Localization

Nabhan

Ribeiro

2006

Journal of Biological Chemistry

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The AP1 (activator protein 1) transcription factor, c-Jun, is an important regulator of cell proliferation, differentiation, survival, and death. Its activity is regulated both at the level of transcription and post-translationally through phosphorylation, sumoylation, and targeted degradation. The degradation of c-Jun by the ubiquitin proteasome pathway has been well established. Here, we report that POH1, a subunit of the 19 S proteasome lid with a recently described deubiquitinase activity, is a regulator of c-Jun. Ectopic expression of POH1 in HEK293 cells decreased the level of c-Jun ubiquitination, leading to significant accumulation of the protein and a corresponding increase in AP1-mediated gene expression. The stabilization also correlated with a redistribution of c-Jun in the nucleus. These effects were reduced by mutation of a cysteine residue in the Mpr1 pad1 N-terminal plus motif of POH1 (Cys-120) and appeared to be selective for c-Jun, because POH1 had no effect on other proteasomal substrates. Our results identify a novel mechanism of c-Jun regulation in mammalian cells.The 26 S proteasome is the principal site of controlled protein degradation in eukaryotic cells. The 2-to 2.5-MDa proteasome complex consists of a central core (20 S proteasome) and one or two multiprotein regulatory particles (RPs 2 ; 19 S proteasome), which are further organized into base and lid regions (1). The 19 S RP mediates the binding, deubiquitination, and unfolding of substrates into the 20 S core, where proteolysis takes place (2). One of the many cellular proteins targeted for degradation by the proteasome is the AP1 transcription factor, c-Jun (3). In addition to being the most potent transcriptional activator of its group, c-Jun is involved in a myriad of cellular activities, including tumorigenesis (4). Tight control of intracellular concentrations of active c-Jun is therefore required, a process that is achieved through rapid turnover by ubiquitination and degradation. Novel mechanisms for targeted ubiquitination of c-Jun were recently shown to be carried out by c-Jun-specific ubiquitin ligases, such as Itch (5) and SCF Fbw7 (6). Whereas much continues to be learned about mechanisms of c-Jun ubiquitination, little is known about the process of deubiquitination and its contribution to the overall regulation of c-Jun. Cellular deubiquitinases (DUBs) play an important role in controlled protein degradation (7); when bound to the proteasome they mediate the removal of ubiquitin chains as the substrate is being degraded, a step that facilitates substrate translocation into the 20 S chamber and allows for recycling of ubiquitin in the cell. DUBs also provide ubiquitin-editing activity, which can rescue particular substrates from being degraded by removing or trimming the degradation signal. A wide range of DUBs has been identified in eukaryotic cells, including enzymes with specificities for particular ubiquitinated substrates (8) but no specific c-Jun deubiquitinase activity has yet been reported.A number of studies hav...

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Section: Discussionmentioning

confidence: 99%

The 19 S Proteasomal Subunit POH1 Contributes to the Regulation of c-Jun Ubiquitination, Stability, and Subcellular Localization

Nabhan

Ribeiro

2006

Journal of Biological Chemistry

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“…Unlike normal cells, several cancer cells show aberrant increased proteasomal activity that promotes the degradation of tumor suppressor proteins and cell cycle proteins favoring cancer cell survival, high proliferation rates, and development of drug resistance (72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82). In our present work, to further examine whether the changes in the relative abundance of proteasome subunits induced by CS accounted for changes in the proteasome activity, the chymotrypsin-like activity of the proteasome was assessed in cells after diterpenes exposure for different times (2, 6 and 24 h).…”

Section: ϫ132mentioning

confidence: 99%

Nano-liquid Chromatography-orbitrap MS-based Quantitative Proteomics Reveals Differences Between the Mechanisms of Action of Carnosic Acid and Carnosol in Colon Cancer Cells

Valdés

García‐Cañas

Artemenko

et al. 2017

Molecular & Cellular Proteomics

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Carnosic acid (CA) and carnosol (CS) are two structurally related diterpenes present in rosemary herb (Rosmarinus officinalis). Although several studies have demonstrated that both diterpenes can scavenge free radicals and interfere in cellular processes such as cell proliferation, they may not necessarily exert the same effects at the molecular level. In this work, a shotgun proteomics study based on stable isotope dimethyl labeling (DML) and nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) has been performed to identify the relative changes in proteins and to gain some light on the specific molecular targets and mechanisms of action of CA and CS in HT-29 colon cancer cells. Protein profiles revealed that CA and CS induce different Nrf2-mediated response. Furthermore, examination of our data revealed that each diterpene affects protein homeostasis by different mechanisms. CA treatment induces the expression of proteins involved in the unfolded protein response in a concentration dependent manner reflecting ER stress, whereas CS directly inhibits chymotrypsin-like activity of the 20S proteasome. In conclusion, the unbiased proteomics-wide method applied in the present study has demonstrated to be a powerful tool to reveal differences on the mechanisms of action of two related bioactive compounds in the same biological model. Molecular &

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“…In the same method, fr. 4 (13.4 g) was subjected to Sephadex LH-20 and eluted with MeOH (4.5 L) to give 5,6,3′,4′-tetrahydroxy-7-methoxyflavone (8,19.0 mg) [29]. The fr.…”

Section: Extraction and Isolationmentioning

confidence: 99%

5,6,3′,4′-Tetrahydroxy-7-methoxyflavone as a Novel Potential Proteasome Inhibitor

Chang

Ding²,

Teng³

et al. 2010

Planta Med

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Proteasome inhibition is one of the new pharmaceutical approaches to study antitumor activity. Although the active components are not yet identified for either treating or preventing cancer, the low toxicity plant Anisomeles ovata R. Br. has been used in traditional herbal medicine for more than 1000 years. In this study, the methanol extract from Anisomeles ovata showed potent inhibition of proteasome activity. Twenty compounds, two macrocycylic diterpenoids, six aromatics, seven flavonoids, and five phenylethanoids were isolated from Fang Feng Cao the dried aerial parts of A. ovata. Their structures have been established on the basis of spectral evidence. Using a proteolysis assay for inhibition of 26S proteasome from pig red blood cells, we found that 5,6,3',4'-tetrahydroxy-7-methoxyflavone inhibited 90.5 %, 85.4 % and 73.1 % the chymotrypsin-like, caspase-like and trypsin-like activities of 26S proteasome with IC (50) values of 14.0, 5.4 and 24.1 microM, respectively, when Suc-LLVY-AMC, Z-LLE-AMC and Ac-RLR-AMC were used as substrates. 5,6,3',4'-Tetrahydroxy-7-methoxyflavone had a higher inhibitory at 15 minutes. A combination of 5,6,3',4'-tetrahydroxy-7-methoxyflavone and 5,6,4'-trihydroxy-7,3'-dimethoxyflavone increased the inhibition ability on 26S enzymatic activity. This combination appears to be a potentially attractive chemotherapy approach. We have found that 5,6,3',4'-tetrahydroxy-7-methoxyflavone has the highest inhibitory effects on 26S proteasome activities when compared to the other 11 flavonoids. These results suggest that both the 6-hydroxy and 7-methoxy positions of the flavone may play an important role in targeting 26S proteasome activity.

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Expression of proteasomal proteins in ten different tumor cell lines

Cited by 19 publications

References 30 publications

The 19 S Proteasomal Subunit POH1 Contributes to the Regulation of c-Jun Ubiquitination, Stability, and Subcellular Localization

The 19 S Proteasomal Subunit POH1 Contributes to the Regulation of c-Jun Ubiquitination, Stability, and Subcellular Localization

Nano-liquid Chromatography-orbitrap MS-based Quantitative Proteomics Reveals Differences Between the Mechanisms of Action of Carnosic Acid and Carnosol in Colon Cancer Cells

5,6,3′,4′-Tetrahydroxy-7-methoxyflavone as a Novel Potential Proteasome Inhibitor

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