cbl-3: a new mammalian cbl family protein

Keane, Maccon M.; Ettenberg, Seth A.; Nau, Marion M.; Banerjee, Priya R.; Cuello, Mauricio; Penninger, Josef; Lipkowitz, Stan

doi:10.1038/sj.onc.1202753

Cited by 128 publications

(152 citation statements)

References 40 publications

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“…The rapid removal of growth factor receptors from the cell surface, and subsequent targeting to lysosomal degradative compartments, provides a down-regulation mechanism important for preventing sustained activation of signaling pathways, which could potentially lead to cellular transformation (reviewed in Marmor and Yarden, 2004). Receptor downregulation is dependent on RTK activation and ubiquitination (Katzmann et al, 2001;Buchberger, 2002;Davies et al, 2004) by the Cbl family of ubiquitin ligases (Joazeiro et al, 1999;Yokouchi et al, 1999;Keane et al, 1999;Thien and Langdon, 2001).…”

Section: Regulation Of Met Downregulation: Consequence For Oncogenic mentioning

confidence: 99%

From Tpr-Met to Met, tumorigenesis and tubes

2007

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The receptor for hepatocyte growth factor (HGF)/scatter factor (SF), Met, controls a program of invasive epithelial growth through the coordination of cell proliferation and survival, cell migration and epithelial morphogenesis. This process is important during embryogenesis and for organ regeneration in the adult. However, when deregulated the HGF/SF-Met signaling axis contributes to tumorigenesis and metastasis. Studies on the oncogenic activation of the Met receptor have shed light on the molecular mechanisms underlying the oncogenic activation of receptor tyrosine kinase (RTKs). More than a decade ago, work on the Met related oncogene, Tpr-Met, revealed the mechanism for activation of RTK-derived oncogenes generated following chromosomal translocation. More recently, studies on the mechanisms of downregulation of the Met RTK highlight a role for loss of downregulation in RTK oncogenic activation.

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Section: Regulation Of Met Downregulation: Consequence For Oncogenic mentioning

confidence: 99%

From Tpr-Met to Met, tumorigenesis and tubes

2007

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“…The Cbl proteins (Cbl, Cbl-b, and Cbl-c) are negative regulators of WT EGFR signaling (Ettenberg et al, 1999a(Ettenberg et al, , b, 2001Keane et al, 1999;Levkowitz et al, 1999;Waterman et al, 1999a;Yokouchi et al, 1999;Duan et al, 2003). The Cbl proteins all contain an aminoterminal TK-binding (TKB) domain, a RING finger domain, and a region of proline-rich sequences in their carboxy-terminus (Nau and Lipkowitz, 2003).…”

Section: Introductionmentioning

confidence: 99%

EGFRvIII undergoes activation-dependent downregulation mediated by the Cbl proteins

et al. 2006

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The overexpression or mutation of tyrosine kinases (TKs), such as the epidermal growth factor receptor (EGFR), can lead to the development of cancer. The most common mutation of the EGFR in glioblastomas is the deletion of exons 2-7 known as the EGFRvIII. This mutant receptor cannot bind EGF but, instead, is constitutively active. The Cbl family of ubiquitin ligases (Cbl, Cbl-b, and Cbl-c) targets the activated EGFR for degradation. As the EGFRvIII is transforming, we investigated whether it could be downregulated by the Cbl proteins. The over-expression of all three Cbl proteins resulted in the ubiquitination and degradation of the EGFRvIII. As with the wild-type EGFR, the TK-binding domain and the RING finger of Cbl-b are sufficient for the downregulation of the EGFRvIII. Also, we found that Cbl-b is recruited to the EGFRvIII and inhibits the transformation of NIH 3T3 cells by the EGFRvIII. Mutation of the Cbl-binding site (Y1045F) in the EGFRvIII inhibits its ubiquitination and downregulation by Cbl-b and enhances its ability to transform. Furthermore, the EGFR TK inhibitor, AG 1478, prevents the downregulation of the EGFRvIII by the Cbl proteins and antagonizes the ability of an immunotoxin directed against the EGFRvIII to kill cells expressing this receptor. In conclusion, the EGFR-vIII does not transform by escaping regulation by Cbl proteins and this activation-induced downregulation of the EGFRvIII has an important role in mediating the toxicity of anti-EGFRvIII immunotoxins.

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“…1). Because TRAIL-R3 is expressed in MCF-7 cells [28,29], total RNA from this cell line was employed. As negative controls, tRNA and total RNA from mouse liver cells were used.…”

Section: Cloning the 5p Upstream Region Of The Human Trail-r3mentioning

confidence: 99%

Transcription initiation sites and promoter structure of the human TRAIL‐R3 gene¹

et al. 2002

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TRAIL-R3 is a decoy receptor for TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), a member of the tumor necrosis factor ligand family. In several cell types decoy receptors inhibit TRAIL-induced apoptosis by binding TRAIL and preventing its binding to TRAIL pro-apoptotic receptors. Here we report the cloning of the promoter region of human TRAIL-R3 and the mapping of the transcriptional start sites. This gene contains a consensus TATA box and the minimal promoter lies within the ¢rst 33 nucleotides upstream of the transcription start site. Transient transfection assays of luciferase reporter plasmids demonstrate that human TRAIL-R3 promoter can be induced in doxorubicin-treated MCF-7 cells in a p53-independent manner. ß

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cbl-3: a new mammalian cbl family protein

Cited by 128 publications

References 40 publications

From Tpr-Met to Met, tumorigenesis and tubes

From Tpr-Met to Met, tumorigenesis and tubes

EGFRvIII undergoes activation-dependent downregulation mediated by the Cbl proteins

Transcription initiation sites and promoter structure of the human TRAIL‐R3 gene¹

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cbl-3: a new mammalian cbl family protein

Cited by 128 publications

References 40 publications

From Tpr-Met to Met, tumorigenesis and tubes

From Tpr-Met to Met, tumorigenesis and tubes

EGFRvIII undergoes activation-dependent downregulation mediated by the Cbl proteins

Transcription initiation sites and promoter structure of the human TRAIL‐R3 gene1

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Transcription initiation sites and promoter structure of the human TRAIL‐R3 gene¹