Negative regulation of FcϵRI-mediated mast cell activation by a ubiquitin-protein ligase Cbl-b

Qu, Xiujuan; Sada, Kiyonao; Kyo, Shinkou; Maeno, Kazuo; Miah, S. M. Shahjahan; Yamamura, Hirohei

doi:10.1182/blood-2003-07-2260

Cited by 74 publications

(88 citation statements)

References 45 publications

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“…Thus, certain drugs that enhance the activity of the Cbl protein family may provide new strategies for cancer therapy (19)(20)(21). Our previous studies found that up-regulation of Cbl-b inhibited Akt and ERK activation, and thus increased the sensitivity of different drugs in gastric cancer and leukemia cells (22,23).…”

Section: Inhibition Of Akt and Erk Enhances β-Elemene-induced Apoptosismentioning

confidence: 99%

Cbl-regulated Akt and ERK signals are involved in β-elemene-induced cell apoptosis in lung cancer cells

et al. 2011

Mol Med Report

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Abstract. β-elemene is an active component of a natural plantderived antineoplastic agent. Although the anticancer activity of β-elemene has been reported, its antitumor mechanism has not been elucidated. The aim of the present study was to investigate how Cbl-regulated Akt and ERK affect β-elemeneinduced cell apoptosis in lung cancer cells. In the present study, β-elemene induced cell apoptosis in a dose-dependent manner in A549 cells. Moreover, β-elemene decreased bcl-2 expression, increased bax expression and caused the cleavage of PARP. However, β-elemene also induced the phosphorylation of Akt and ERK in a short period of time. The inhibition of Akt and ERK activation rapidly enhanced β-elemene-induced apoptosis, and the up-regulation of c-Cbl and Cbl-b expression was also detected. These results suggest that Cbl-regulated Akt and ERK signals are involved in β-elemene-induced cell apoptosis in lung cancer cells.

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Section: Inhibition Of Akt and Erk Enhances β-Elemene-induced Apoptosismentioning

confidence: 99%

Cbl-regulated Akt and ERK signals are involved in β-elemene-induced cell apoptosis in lung cancer cells

et al. 2011

Mol Med Report

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“…RBL-2H3 cells overexpressing DN Cbl-b have been used in previous studies (27,30). It was observed that p-Akt expression is slightly increased in Cbl-b (DN) overexpressing cells.…”

Section: Cbl-b Enhanced Ato-induced Apoptosismentioning

confidence: 99%

“…Rat basophilic leukemia RBL-2H3 cells and cells overexpressing a dominant negative (DN) Cbl-b mutation (27) were maintained as monolayer cultures in Dulbecco's modified Eagle's medium (DMEM) containing 100 U/mL penicillin and 10% heat-inactivated FBS (27). The transfected cells were cultured in the presence of 0.4 mg/mL G418 (USA).…”

Section: Cell Culturementioning

confidence: 99%

E3 ubiquitin ligase Cbl-b potentiates the apoptotic action of arsenic trioxide by inhibiting the PI3K/Akt pathway

Li¹,

Qu²,

Qu³

et al. 2011

Braz J Med Biol Res

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Arsenic trioxide (ATO) is a strong inducer of apoptosis in malignant hematological cells. Inducible phosphatidyl inositol 3 kinase (PI3K)-Akt activation promotes resistance to ATO. In the present study, we evaluated whether E3 ubiquitin ligase Cbl-b, a negative regulator of PI3K activation, is involved in the action of ATO. The effect of ATO on cell viability was measured by the Trypan blue exclusion assay or by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was determined by flow cytometry and protein expression was assayed by Western blotting. ATO decreased the viability of HL60 cells and induced cellular apoptosis, which was accompanied by transient activation of Akt. The PI3K/Akt inhibitor, LY294002, significantly increased ATO-induced apoptosis (P < 0.05). In addition, ATO up-regulated the expression of Cbl-b proteins. Furthermore, ATO inhibited cell viability with an IC 50 of 18.54 μM at 24 h in rat basophilic leukemia-2H3 cells. ATO induced cellular apoptosis with transient activation of Akt and Cbl-b was also up-regulated. Rat basophilic leukemia-2H3 cells transfected with a dominant negative (DN) Cbl-b mutation showed overexpression of Cbl-b (DN) and enhanced Akt activation. Compared with cells transfected with vector, ATO-induced apoptosis was decreased and G2/M phase cells were increased at the same concentration (P < 0.05). The PI3K/Akt inhibitor, LY294002, re-sensitized Cbl-b (DN) overexpressing cells to ATO and reversed G2/M arrest (P < 0.05). Taken together, these results suggest that Cbl-b potentiates the apoptotic action of ATO by inhibition of the PI3K/Akt pathway.

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“…Some previous surveys showed that Cbl-b sequestered signalling molecules from lipid rafts, which resulted in ineffective lipid raft aggregation in mast cells [18,19].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Analysis and Pathological Assessment of B-Cbl Proto-Oncogene in Gastric Carcinoma Cells

Harir¹

2016

Ann Cytol Pathol

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In order to study the status and expression of Cbl-b oncoprotein in gastric carcinoma we underwent an immunohistochemical protocol by which we analyzed the immuno-distribution as well as the level of Cbl-b expression on gastric cancerous tissues. Material and MethodsNinety-six (96) paraffin blocks of cancerous gastric tissues sections were collected from the Department of pathology of Oran Military Hospital (Western Algeria) for the period of 2006-2015. All the cases were identified histologically as malignant gastric cells. These specimens were paraffin embedded in the same center. The cases were stained with hemotoxyline and eosin (H&E) for routine histological examination. An absolute confidentiality of the patients' vital information was maintained for ethical purposes and an ethical approval was obtained from the institution in which the study was carried out. Immunohistochemical protocolWe used the following Abcam protocol of immunohistochemistry (IHC): formalin-fixed paraffin-embedded tissue sections were deparaffinized and rehydrated then enough drops of Hydrogen Peroxide Block were added to cover the sections, they were incubated for 10 minutes then washed twice in buffer Phosphate Buffered Saline (PBS) (10X PBS) (0.1M PBS, pH 7.4).A pretreatment was performed then the sections were washed 3 times in buffer. IntroductionGastric cancer is becoming a major health problem worldwide because of the lack of effective biomarkers for metastasis prediction [1].The mammalian Cbl protein down regulation was implicated in gastric cancer development [2]. Cbl family consists of the three homologues c-Cbl, Cbl-b, and Cbl-3, all of which associate with a wide variety of signaling proteins [3].Through these many associations, Cbl is able to regulate diverse signaling networks; one of the most extensively studied roles of Cbl is its function as a negative regulator of receptor tyrosine kinase (RTK) signaling [4][5][6].Cbl-b is a second member of the E3 ubiquitin ligase Cbl family, some studies have revealed that Cbl-b regulates gastric cancer cell proliferation, drug sensitivity and also migration [1,7,8]. In addition, Cbl-b can degrade as well IGF-I signaling intermediate IRS-1 and decrease protein synthesis in unloading-induced muscle atrophy [9]. Some surveys showed that the p85 regulatory subunit of PI3 kinase (PI3K) serves a substrate for Cbl-b during activation of T cells and Cbl-b functions as a negative regulator of p85 in a ubiquitindependent but proteolysis-independent manner [10,11]. Cbl-bdeficient inhibited Akt and ERK phosphorylation and deregulation of T cell proliferation [12,14]. Research AbstractObjective: In order to study the status and the expression of Cbl-b onco-protein in gastric carcinoma we underwent an immunohistochemical protocol by which we analyzed the immunodistribution as well as the level of Cbl-b expression on gastric cancerous tissues. Results: Our immunohistochemical analysis revealed that Cbl-b protein was expressed in gastric cancerous cells with different immune-scoring and differ...

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Negative regulation of FcϵRI-mediated mast cell activation by a ubiquitin-protein ligase Cbl-b

Cited by 74 publications

References 45 publications

Cbl-regulated Akt and ERK signals are involved in β-elemene-induced cell apoptosis in lung cancer cells

Cbl-regulated Akt and ERK signals are involved in β-elemene-induced cell apoptosis in lung cancer cells

E3 ubiquitin ligase Cbl-b potentiates the apoptotic action of arsenic trioxide by inhibiting the PI3K/Akt pathway

Immunohistochemical Analysis and Pathological Assessment of B-Cbl Proto-Oncogene in Gastric Carcinoma Cells

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