Profiling of nuclear extract proteins from human neuroblastoma cell lines: the search for fingerprints

Escobar, Mauricio A.; Hoelz, Derek J.; Sandoval, John A.; Hickey, Robert J.; Grosfeld, Jay L.; Malkas, Linda H.

doi:10.1016/j.jpedsurg.2004.10.032

Cited by 17 publications

(11 citation statements)

References 47 publications

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“…Currently, the search for biomarkers to diagnose tumor presence and determine prognosis in advanced NB dominates the literature [12][13][14][15][16][17][18][19][20][21][22][23][24][25]. However, reports on long-term outcomes in stage IV NB are relatively infrequent.…”

Section: Discussionmentioning

confidence: 99%

Long-term outcomes in patients with stage IV neuroblastoma

Escobar

Grosfeld

Powell

et al. 2006

Journal of Pediatric Surgery

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Section: Discussionmentioning

confidence: 99%

Long-term outcomes in patients with stage IV neuroblastoma

Escobar

Grosfeld

Powell

et al. 2006

Journal of Pediatric Surgery

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“…As a consequence, GA has been evaluated and developed as a potential chemotherapeutic agent and GA analogues have recently completed Phase-I clinical trials in adult and paediatric tumours and the paediatric tumour neuroblastoma (NB) identified for potential future GAanalogue chemotherapy (Lo`pez-Maderuelo et al, 2001;Kim et al, 2003;Escobar et al, 2005;Graner and Bigner, 2005;Grem et al, 2005;Bagatell et al, 2007;Erdmann et al, 2007;Ramanathan et al, 2007;Shen et al, 2007;Solit et al, 2007;Weigel et al, 2007;Xu and Neckers, 2007).…”

Section: Introductionmentioning

confidence: 99%

The neuroblastoma tumour-suppressor TrkAI and its oncogenic alternative TrkAIII splice variant exhibit geldanamycin-sensitive interactions with Hsp90 in human neuroblastoma cells

et al. 2009

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Hsp90 chaperones stabilize many tyrosine kinases including several oncogenes, which are inhibited or induced to degrade by the Hsp90 inhibitor geldanamycin (GA). As a consequence, GA has been developed for future chemotherapeutic use in several tumour types including neuroblastoma (NB). Alternative splicing of the neurotrophin receptor tyrosine kinase TrkA may have a pivotal function in regulating NB behaviour, with reports suggesting that tumour-suppressing signals from TrkA may be converted to oncogenic signals by stress-regulated alternative TrkAIII splicing. Within this context, it is important to know whether Hsp90 interacts with TrkA variants in NB cells and how GA influences this. Here, we report that both TrkAI and TrkAIII are Hsp90 clients in human NB cells. TrkAI exhibits GA-sensitive interaction with Hsp90 required for receptor endoplasmic reticulum export, maturation, cell surface stabilization and ligandmediated activation, whereas TrkAIII exhibits GAsensitive interactions with Hsp90 required for spontaneous activity and to a lesser extent stability. We show that GA inhibits proliferation and induces apoptosis of TrkAI expressing NB cells, whereas TrkAIII reduces the sensitivity of NB cells to GA-induced elimination. Our data suggest that GA-sensitive interactions with Hsp90 are critical for both TrkAI tumour suppressor and TrkAIII oncogenic function in NB and that TrkAIII expression exerts a negative impact on GA-induced NB cell eradication, which can be counteracted by a novel TrkAIII-specific peptide nucleic acid inhibitor.

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“…Proteomics has been successfully applied to a number of organelles, however, studies of the mammalian nucleus have been relatively limited (23)(24)(25)(26)(27) with most restricted to nuclear protein complexes (28 -35). A common challenge for nuclear proteomics studies is the difficulty of isolating this highly interconnected organelle with sufficient purity (36).…”

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confidence: 99%

Specialized compartments of cardiac nuclei exhibit distinct proteomic anatomy

Franklin¹,

Zhang²,

Chen³

et al. 2011

Molecular & Cellular Proteomics

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As host to the genome, the nucleus plays a critical role as modulator of cellular phenotype. To understand the totality of proteins that regulate this organelle, we used proteomics to characterize the components of the cardiac nucleus. Following purification, cardiac nuclei were fractionated into biologically relevant fractions including acid-soluble proteins, chromatin-bound molecules and nucleoplasmic proteins. These distinct subproteomes were characterized by liquid chromatography-tandem MS. We report a cardiac nuclear proteome of 1048 proteins-only 146 of which are shared between the distinct subcompartments of this organelle. Analysis of genomic loci encoding these molecules gives insights into local hotspots for nuclear protein regulation. High mass accuracy and complementary analytical techniques allowed the discrimination of distinct protein isoforms, including 54 total histone variants, 17 of which were distinguished by unique peptide sequences and four of which have never been detected at the protein level. These studies are the first unbiased analysis of cardiac nuclear subcompartments and provide a foundation for exploration of this organelle's proteomes during disease. Molecular & Cellular

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Profiling of nuclear extract proteins from human neuroblastoma cell lines: the search for fingerprints

Cited by 17 publications

References 47 publications

Long-term outcomes in patients with stage IV neuroblastoma

Long-term outcomes in patients with stage IV neuroblastoma

The neuroblastoma tumour-suppressor TrkAI and its oncogenic alternative TrkAIII splice variant exhibit geldanamycin-sensitive interactions with Hsp90 in human neuroblastoma cells

Specialized compartments of cardiac nuclei exhibit distinct proteomic anatomy

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