Downregulation of epidermal growth factor receptor signaling by singlet oxygen through activation of caspase-3 and protein phosphatases

Zhuang, Songlin; Ouédraogo, Gladys D.; Kochevar, Irene E.

doi:10.1038/sj.onc.1206604

Cited by 47 publications

(42 citation statements)

References 62 publications

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“…It appears that downregulation of EGFR upon executing caspase activation is a generic reaction rather than stimulus or cell typespecific. Similar downregulation by active caspases may also hold true for some other receptor tyrosine kinases (RTKs) such as Neu, another member of the EGFR family and PDGFR (Zhuang et al, 2003;Tulasne et al, 2004). Those RTKs seem to be the cleavage targets for activated caspases, confirming the execution function of caspases to assure cell death.…”

Section: Discussionmentioning

confidence: 72%

“…EGFR downregulation during apoptosis is neither stimulispecific nor cell-type-specific To determine whether other stimuli have a similar effect in addition to tumor necrosis factor-a (TNF-a)/cycloheximide (CHX), photosenstization of rose Bengal, and ultraviolet A (UVA), ultraviolet B (UVB) and ultraviolet C (UVC) (Bae et al, 2001;He et al, 2003a;Zhuang et al, 2003), we treated HaCaT cells for 6 h with actinomycin D (AD, 10 mM), camptothecin (CA, 2 mM), cycloheximide (CY, 100 mM), etoposide, (EP, 100 mM), paclitaxel (PA, 2 mg/ml), staurosporine (ST, 0.5 mg/ml), doxorubicin hydrochloride (DX, 5 mg/ ml), or puromycin dihydrochloride (PU, 20 mg/ml). All of these treatments caused caspase-3 activation and parallel EGFR downregulation (Figure 1a).…”

Section: Resultsmentioning

confidence: 99%

“…EGFR signaling serves as one of the critical survival signals, which may become the target of caspase activation, in order to assure the execution of apoptosis. EGFR was down-regulated in response to apoptosis by a few treatments (Bae et al, 2001;He et al, 2003a;Zhuang et al, 2003). However, whether EGFR was a direct substrate of caspases in vivo and the mechanism involved remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Cleavage of epidermal growth factor receptor by caspase during apoptosis is independent of its internalization

Huang

2005

Oncogene

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Section: Discussionmentioning

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cleavage of epidermal growth factor receptor by caspase during apoptosis is independent of its internalization

Huang

2005

Oncogene

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“…Caspase inhibition does not affect gemcitabine-induced EGFR degradation EGFR downregulation can occur rapidly following caspase activation, independent of receptor phosphorylation or ubiquitination (He et al, 2003;Zhuang et al, 2003). Although our results suggested that gemcitabine downregulates EGFR along a different pathway, one which requires receptor phosphorylation and proteosomal/lysosomal processing, we wanted to determine if activated caspase contributed to gemcitabine-triggered EGFR degradation.…”

Section: Blockade Of Egfr Degradation Reduces Gemcitabinemediated Clomentioning

confidence: 94%

“…Recently, theaflavin-3,3 0 -digallate, a derivative from black tea, was demonstrated to trigger EGFR degradation along a proteosome/lysosome pathway, which is independent of receptor phosphorylation (Mizuno et al, 2005). Several agents, such as ultraviolet A light and singlet oxygen, result in EGFR degradation as a nonspecific target in caspase activation (He et al, 2003;Zhuang et al, 2003). Of all the agents discussed, only gemcitabine has been demonstrated to induce EGFR degradation along a pathway similar to EGF-induced receptor downregulation.…”

Section: Figurementioning

confidence: 99%

Role of epidermal growth factor receptor degradation in gemcitabine-mediated cytotoxicity

et al. 2006

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We have recently reported that treatment with gemcitabine, a potent chemotherapeutic agent and radiation sensitizer, stimulates phosphorylation of the epidermal growth factor receptor (EGFR). Because phosphorylation of EGFR is known to precede receptor degradation, we hypothesized that gemcitabine treatment may also result in EGFR degradation. In two human head and neck cancer cell lines, UMSCC-1 and UMSCC-6, we demonstrated an approximately 80% decrease in total EGFR levels at 72 h after a 2-h treatment with 1 lM gemcitabine. Neither cisplatin nor 5-fluorouracil, which are used to treat head and neck cancer, caused EGFR degradation. EGFR downregulation did not occur at the level of transcription, as assessed by reverse transcription-polymerase chain reaction (RT-PCR), but instead occurred via phosphorylation and ubiquitination of the receptor along a proteosome/lysosome-mediated pathway. Inhibition of EGFR degradation, by either pretreatment with the EGFR tyrosine kinase inhibitor gefitinib or by exposure to the proteosome/lysosome inhibitor MG132, significantly reduced gemcitabine-induced cell death. These results suggest that EGFR degradation may be a novel mechanism for gemcitabine-mediated cell death. These findings also indicate that caution should be exercised when combining gemcitabine with agents that may prevent EGFR degradation, such as EGFR tyrosine kinase inhibitors administered in a suboptimal sequence or proteosome inhibitors.

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Single cell analysis of PKC activation during proliferation and apoptosis induced by laser irradiation

Gao

Chen

Xing

et al. 2005

Journal Cellular Physiology

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Laser irradiation has been shown to trigger cellular proliferation and apoptosis in various cell types. Studying the signaling pathways involved in the laser irradiation is important for understanding these processes. In present study, to monitor the protein kinase Cs (PKCs) activity in living cells in real time, we transfected and screened human lung adenocarcinoma cells (ASTC-a-1) stably expressing C kinase activity reporter (CKAR) constructed based on fluorescence resonance energy transfer (FRET) technique. The CKAR is a specific, reversible reporter of phosphorylation by PKCs and it can monitor the ongoing balance between PKCs and phosphatases. The increasing dynamics of PKCs activity is monitored during cell proliferation induced by low-power laser irradiation (LPLI) (0.8 J/cm2) in serum-starved ASTC-a-1 cells stably expressing CKAR reporter using FRET imaging on laser scanning confocal microscope and using spectrofluorometric analysis on a luminescence spectrometer, respectively. However, the decreasing dynamics of PKCs activity has been monitored in real time using FRET imaging for the cells treated with high fluence LPLI (60 J/cm2), which was previously found to induce cell apoptosis. Taken together, LPLI induces the ASTC-a-1 cell proliferation by specifically activating PKCs. However, PKCs activity decreases during cell apoptosis induced by high fluence LPLI. Our results indicate that PKCs play an important role in the laser irradiation-induced biological effects.

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Downregulation of epidermal growth factor receptor signaling by singlet oxygen through activation of caspase-3 and protein phosphatases

Cited by 47 publications

References 62 publications

Cleavage of epidermal growth factor receptor by caspase during apoptosis is independent of its internalization

Cleavage of epidermal growth factor receptor by caspase during apoptosis is independent of its internalization

Role of epidermal growth factor receptor degradation in gemcitabine-mediated cytotoxicity

Single cell analysis of PKC activation during proliferation and apoptosis induced by laser irradiation

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