TACE-Mediated Ectodomain Shedding of the Type I TGF-β Receptor Downregulates TGF-β Signaling

Liu, Cheng; Xu, Pinglong; Lamouille, Samy; Xu, Jian; Derynck, Rik

doi:10.1016/j.molcel.2009.06.018

Cited by 125 publications

(132 citation statements)

References 47 publications

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“…14) ERK and p38 MAP kinase regulate the TACE-mediated ectodomain shedding of cell-surface proteins. [19][20][21]27) Consistent with this notion, we have previously shown that both ERK and p38 MAP kinase are responsible for the TNF receptor 1 shedding induced by acetoxycycloheximide, cytotrienin A and deoxynivalenol in A549 cells. 13,14,22) However, unlike these translation inhibitors, our results revealed that only ERK is responsible for the TNF receptor 1 shedding induced by irciniastatin A.…”

Section: Resultssupporting

confidence: 61%

Irciniastatin A Induces Potent and Sustained Activation of Extracellular Signal-Regulated Kinase and Thereby Promotes Ectodomain Shedding of Tumor Necrosis Factor Receptor 1 in Human Lung Carcinoma A549 Cells

Quach

Hirano

Fukuhara

et al. 2015

Biological & Pharmaceutical Bulletin

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Irciniastatin A is a pederin-type marine product that potently inhibits translation. We have recently shown that irciniastatin A induces ectodomain shedding of tumor necrosis factor (TNF) receptor 1 with slower kinetics than other translation inhibitors. In human lung carcinoma A549 cells, irciniastatin A induced a marked and sustained activation of extracellular signal-regulated kinase (ERK) and induced little activation of p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK). Moreover, the TNF receptor 1 shedding induced by irciniastatin A was blocked by the MAP kinase/ERK kinase inhibitor U0126, but not by the p38 MAP kinase inhibitor SB203580 or the JNK inhibitor SP600125. Thus unlike other translation inhibitors that trigger ribotoxic stress response, our results show that irciniastatin A is a unique translation inhibitor that induces a potent and sustained activation of the ERK pathway, and thereby promotes the ectodomain shedding of TNF receptor 1 in A549 cells.Key words irciniastatin A; extracellular signal-regulated kinase; translation inhibitor; tumor necrosis factor receptor 1; ribotoxic stress response; p38 mitogen-activated protein kinase Irciniastatin A, also known as psymberin (Fig. 1A), is a marine natural product originally isolated from the marine sponges Ircinia ramose and Psammocinia.

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Section: Resultssupporting

confidence: 61%

Irciniastatin A Induces Potent and Sustained Activation of Extracellular Signal-Regulated Kinase and Thereby Promotes Ectodomain Shedding of Tumor Necrosis Factor Receptor 1 in Human Lung Carcinoma A549 Cells

Quach

Hirano

Fukuhara

et al. 2015

Biological & Pharmaceutical Bulletin

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“…ADAM17 contributes to downregulate TGFb signaling through at least two different but complementary mechanisms. In addition to the VASN-dependent mechanism described here, ADAM17 can inhibit TGFb signaling by cleaving the TbRI (Liu et al, 2009). Thus, in addition to cleave and activate a ligand trap, ADAM17 depletes the cell surface from one of the components of the TGFb signaling complex.…”

Section: Regulation Of Protein Function By Adam17mentioning

confidence: 91%

ADAM17 (TACE) regulates TGFβ signaling through the cleavage of vasorin

et al. 2010

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The activity of a variety of extracellular signaling factors is tightly regulated by proteins containing A Disintegrin And a Metalloprotease domain (ADAM) metalloproteases through limited proteolysis. Thus, the identification of ADAM substrates may unveil novel components and mechanisms of cell signaling pathways. We report the identification of the transmembrane protein vasorin (VASN), a transforming growth factor-b (TGFb) trap, as a substrate of ADAM17. The metalloprotease efficiently generates a soluble fragment encompassing the extracellular domain of VASN. Despite the importance of TGFb in normal development and tumor progression, the regulation of VASN is completely unknown. Here, we show that only the soluble form of VASN inhibits TGFb and that the secretion of VASN is tightly controlled by ADAM17. Hence, inhibition of ADAM17 leads to the upregulation of TGFb signaling. Adding a new level of complexity to the function of ADAM17, we finally show that, through the cleavage of VASN, the metalloprotease controls TGFb-mediated epithelial-to-mesenchymal transition.

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“…3f). Conversely, DN-ADAM17 (E406A; point mutation at metalloprotease domain) 27 inhibited S1P-induced responses (Fig. 3g).…”

Section: S1p Increases Adam17 Activity Without Notch Ligandsmentioning

confidence: 95%

Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation

et al. 2014

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Many tumours originate from cancer stem cells (CSCs), which is a small population of cells that display stem cell properties. However, the molecular mechanisms that regulate CSC frequency remain poorly understood. Here, using microarray screening in aldehyde dehydrogenase (ALDH)-positive CSC model, we identify a fundamental role for a lipid mediator sphingosine-1-phosphate (S1P) in CSC expansion. Stimulation with S1P enhances ALDH-positive CSCs via S1P receptor 3 (S1PR3) and subsequent Notch activation. CSCs overexpressing sphingosine kinase 1 (SphK1), an S1P-producing enzyme, show increased ability to develop tumours in nude mice, compared with parent cells or CSCs. Tumorigenicity of CSCs overexpressing SphK1 is inhibited by S1PR3 knockdown or S1PR3 antagonist. Breast cancer patient-derived mammospheres contain SphK1 þ /ALDH1 þ cells or S1PR3 þ /ALDH1 þ cells. Our findings provide new insights into the lipid-mediated regulation of CSCs via Notch signalling, and rationale for targeting S1PR3 in cancer.

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TACE-Mediated Ectodomain Shedding of the Type I TGF-β Receptor Downregulates TGF-β Signaling

Cited by 125 publications

References 47 publications

Irciniastatin A Induces Potent and Sustained Activation of Extracellular Signal-Regulated Kinase and Thereby Promotes Ectodomain Shedding of Tumor Necrosis Factor Receptor 1 in Human Lung Carcinoma A549 Cells

Irciniastatin A Induces Potent and Sustained Activation of Extracellular Signal-Regulated Kinase and Thereby Promotes Ectodomain Shedding of Tumor Necrosis Factor Receptor 1 in Human Lung Carcinoma A549 Cells

ADAM17 (TACE) regulates TGFβ signaling through the cleavage of vasorin

Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation

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