Extracellular HSP90: Conquering the cell surface

Sidera, Katerina; Patsavoudi, Evangelia

doi:10.4161/cc.7.11.6054

Cited by 71 publications

(61 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The potential role of cell-surface Hsp90 in cancer-cell proliferation has recently been highlighted (Tsutsumi and Neckers 2007;Sidera and Patsavoudi 2008). The results of the present study demonstrate the cell-surface expression of Hsp90 in neuroblastoma NB69 cells, particularly in proliferative cells.…”

Section: Discussionsupporting

confidence: 62%

Expression of heat shock protein 90 at the cell surface in human neuroblastoma cells

Cid

Regidor

Poveda

et al. 2009

Cell Stress and Chaperones

View full text Add to dashboard Cite

In addition to the activity of heat shock protein 90 (Hsp90/HSPC) as a chaperone, some recent studies have reported expression of Hsp90 at the cell surface in certain types of cancer and nervous system cells. We study the expression of Hsp90 at the cell surface in human neuroblastoma (NB69) cells. Immunofluorescence experiments labeling with anti-Hsp90 antibodies on both nonpermeabilized cells and live cells detected Hsp90 at the cell surface. Hsp90 was also identified in a membrane fraction from subcellular fractionation. Cell-surface Hsp90 was significantly more expressed in undifferentiated proliferative spherical neuroblastoma cells than in differentiated flattened cells. In addition, spherical cells were significantly more sensitive to Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin compared to flattened cells. This paper describes the first evidence of cell-surface Hsp90 expression in a cancer cell line from nervous tissue and may indicate a novel target for anti-tumoral agents.

show abstract

Section: Discussionsupporting

confidence: 62%

Expression of heat shock protein 90 at the cell surface in human neuroblastoma cells

Cid

Regidor

Poveda

et al. 2009

Cell Stress and Chaperones

View full text Add to dashboard Cite

show abstract

“…Hop can be phosphorylated by cell cycle kinases, phosphorylation by cdc2 (cell division cycle 2) kinase promotes cytoplasmic retention, whereas phosphorylation by casein kinase II (CKII) promotes nuclear Hop, suggesting that Hop might move between the cytoplasm and the nucleus under certain cell cycle conditions [40,41]. The nuclear accumulation of Hop is primarily stress regulated and CKII phosphorylation has been shown not to disrupt Hop-Hsp90 binding [36]. Longshaw et al [42] reported that in the absence of Hop, soluble pYStat3 levels are decreased and accumulation of Stat3 occurs outside the nucleus in mESCs, suggesting that Hop facilitates phosphorylation and transport of Stat3 into the mESCs nucleus.…”

Section: Discussionmentioning

confidence: 99%

“…Webb et al [34] showed that geldanamycin (GA) down regulates MET expression at nanamolar concentrations, thus inhibiting HGF/SF-mediated cell motility and invasion. Another Hsp90 client protein, HER2 has been proposed to interact extracellularly with Hsp90 -activating HER2 by heterodimerisation with HER3, leading to actin remodelling and cell motility via activation of signal transduction pathways MAPK and PI3 K-Akt [35,36].…”

Section: Discussionmentioning

confidence: 99%

RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation

et al. 2011

View full text Add to dashboard Cite

Keywords:Hop/STIP1/STI1 (Hsp70/Hsp90-organising protein) Pancreatic cancer Immunohistochemistry In vitro invasion MMP-2 a b s t r a c tWe previously identified Hop as over expressed in invasive pancreatic cancer cell lines and malignant tissues of pancreatic cancer patients, suggesting an important role for Hop in the biology of invasive pancreatic cancer. Hop is a co-chaperone protein that binds to both Hsp70/Hsp90. We hypothesised that by targeting Hop, signalling pathways modulating invasion and client protein stabilisation involving Hsp90-dependent complexes may be altered.In this study, we show that Hop knockdown by small interfering (si)RNA reduces the invasion of pancreatic cancer cells, resulting in decreased expression of the downstream target gene, matrix metalloproteinases-2 (MMP-2). Hop in conditioned media co-immunoprecipitates with MMP-2, implicating a possible extracellular function for Hop. Knockdown of Hop expression also reduced expression levels of Hsp90 client proteins, HER2, Bcr-Abl, c-MET and v-Src. Furthermore, Hop is strongly expressed in high grade PanINs compared to lower PanIN grades, displaying differential localisation in invasive ductal pancreatic cancer, indicating that the localisation of Hop is an important factor in pancreatic tumours.Our data suggests that the attenuation of Hop expression inactivates key signal transduction proteins which may decrease the invasiveness of pancreatic cancer cells possibly through the modulation of Hsp90 activity. Therefore, targeting Hop in pancreatic cancer may constitute a viable strategy for targeted cancer therapy.

show abstract

“…Both proteins are primarily cytoplasmic, but a small fraction (<10%) is also found in the nucleus (8,9). In addition, HSP90α can be expressed at the cell surface and secreted into the extracellular space under metastatic conditions (2,(10)(11)(12). HSP90β is constitutively and ubiquitously expressed, whereas HSP90α is heat inducible and tissue specific (13).…”

mentioning

confidence: 99%

Heat shock protein 90α (HSP90α), a substrate and chaperone of DNA-PK necessary for the apoptotic response

Solier

Kohn²,

Scroggins³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The “apoptotic ring” is characterized by the phosphorylation of histone H2AX at serine 139 (γ-H2AX) by DNA-dependent protein kinase (DNA-PK). The γ-H2AX apoptotic ring differs from the nuclear foci patterns observed in response to DNA-damaging agents. It contains phosphorylated DNA damage response proteins including activated Chk2, activated ATM, and activated DNA-PK itself but lacks MDC1 and 53BP1, which are required to initiate DNA repair. Because DNA-PK can phosphorylate heat shock protein 90α (HSP90α) in biochemical assays, we investigated whether HSP90α is involved in the apoptotic ring. Here we show that HSP90α is phosphorylated by DNA-PK on threonines 5 and 7 early during apoptosis and that both phosphorylated HSP90α and DNA-PK colocalize in the apoptotic ring. We also show that DNA-PK is a client of HSP90α and that HSP90α is required for full DNA-PK activation, γ-H2AX formation, DNA fragmentation, and apoptotic body formation. In contrast, HSP90 inhibition by geldanamycin markedly enhances TRAIL-induced DNA-PK and H2AX activation. Together, our results reveal that HSP90α is a substrate and chaperone of DNA-PK in the apoptotic response. The response of phosphorylated HSP90α to TRAIL and its localization to the γ-H2AX ring represent epigenetic features of apoptosis that offer insights for studying and monitoring nuclear apoptosis.

show abstract

Extracellular HSP90: Conquering the cell surface

Cited by 71 publications

References 48 publications

Expression of heat shock protein 90 at the cell surface in human neuroblastoma cells

Expression of heat shock protein 90 at the cell surface in human neuroblastoma cells

RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation

Heat shock protein 90α (HSP90α), a substrate and chaperone of DNA-PK necessary for the apoptotic response

Contact Info

Product

Resources

About