In vivo degradation of N-myc in neuroblastoma cells is mediated by the 26S proteasome

Bonvini, Paolo; Nguyen, Phuongmai; Trepel, Jane B.; Neckers, Leonard Μ.

doi:10.1038/sj.onc.1201625

Cited by 52 publications

(29 citation statements)

References 39 publications

(55 reference statements)

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“…Unlike the cadherin-associated b-catenin, the cytosolic b-catenin is known to be the sole pool that is tyrosine phosphorylated in the cell. Recent studies demonstrate that tyrosine phosphorylation of b-catenin is correlated with tumor formation and invasiveness (Sommers et al, 1994;Bonvini et al, 2001). We have already reported that in in vitro NIH3T3 cells the level of cytoplasmic bcatenin is negatively influenced by LMW-PTP expression (Taddei et al, 2002).…”

Section: Epha2 Is the Tyrosine Phosphorylated Substrate Of Lmw-ptp Inmentioning

confidence: 99%

LMW-PTP is a positive regulator of tumor onset and growth

et al. 2004

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Low molecular weight protein tyrosine phosphatases (LMW-PTPs) are an enzyme family that plays a key role in cell proliferation control by dephosphorylating/ inactivating both tyrosine kinase receptors (such as PDGF, insulin, and ephrin receptors) and docking proteins (such, as b-catenin) endowed with both adhesion and transcriptional activity. Besides being a frequent event in human tumors, overexpression of LMW-PTP has been recently demonstrated to be sufficient to induce neoplastic transformation. We recently demonstrated that overexpression of LMW-PTP strongly potentiates the stability of cell-cell contacts at the adherens junction level, which powerfully suggests that LMW-PTP may also contribute to cancer invasivity. Focusing on mechanisms by which LMW-PTP is involved in cancer onset and progression, the emerging picture is that LMW-PTP strongly increases fibronectin-mediated cell adhesion and mobility but, paradoxically, decreases cell proliferation. Nevertheless, LMW-PTP-transfected NIH3T3 fibroblasts engrafted in nude mice induce the onset of larger fibrosarcomas, which are endowed with higher proliferation activity as compared to mock-transfected controls. Quite opposite effects have been obtained with engrafted fibroblasts transfected with a dominant-negative form of LMW-PTP. Notably, in sarcoma extracts, LMW-PTP overexpression greatly influences the ephrin A2 (EphA2) but not PDGF receptor or b-catenin tyrosine phosphorylation. The high association of dephosphorylated EphA2 overexpression with most human cancers and our observation that cell growth stimulation by LMW-PTP overexpression is restricted to the in vivo model, strongly suggest that LMW-PTP oncogenic potential is mediated by its EphA2 tyrosine dephosphorylating activity.

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Section: Epha2 Is the Tyrosine Phosphorylated Substrate Of Lmw-ptp Inmentioning

confidence: 99%

LMW-PTP is a positive regulator of tumor onset and growth

et al. 2004

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“…Transcriptional response to stress signals like proteasome inhibitor treatment is a complex process (Palombella et al, 1994;Ichihara and Tanaka, 1995;Firestein and Feuerstein, 1998;Hofmann et al, 1996;Bonvini et al, 1998) with the response of many genes being dependent on crosstalk between signal transduction pathways and cell type speci®c factors.…”

Section: Introductionmentioning

confidence: 99%

Proteasome inhibitor induced gene expression profiles reveal overexpression of transcriptional regulators ATF3, GADD153 and MAD1

et al. 2000

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“…Moreover, drugs of the GA class can reduce the expression of several tyrosine kinase and serine kinase oncogene products, including Her2, Met, Raf, cdk4, and Akt (Schulte and Neckers, 1998;Webb et al, 2000;Ochel et al, 2001;Blagosklonny, 2002;Solit et al, 2002). These drugs act at concentrations in the nanomolar range (nM-GAi) by inhibiting the molecular chaperone HSP90, thereby preventing proper folding of the client oncoproteins, leading to their destabilization (Webb et al, 2000;Bonvini et al, 2001;Ochel et al, 2001).…”

Section: Introductionmentioning

confidence: 99%