The network interaction of the human cytosolic 90kDa heat shock protein Hsp90: A target for cancer therapeutics

Silva, Viviane C. H. da; Ramos, Carlos H.I.

doi:10.1016/j.jprot.2011.12.028

Cited by 74 publications

(48 citation statements)

References 185 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, a follow-up global analysis of protein phosphorylation reveals that a much greater proportion of the phosphoproteome is cancers respond differently to HSP90 inhibitors depending on their molecular background, 1 unbiased genome-and proteome-wide global approaches should help in the identification of molecular biomarkers to enable selection of patients most likely to respond to treatment with HSP90 inhibitors, as well as being of fundamental research value. 6 …”

Section: Introductionmentioning

confidence: 99%

The expanding proteome of the molecular chaperone HSP90

2012

View full text Add to dashboard Cite

T he molecular chaperone HSP90 maintains the activity and stability of a diverse set of "client" proteins that play key roles in normal and disease biology. Around 20 HSP90 inhibitors that deplete the oncogenic clientele have entered clinical trials for cancer. However, the full extent of the HSP90-dependent proteome, which encompasses not only clients but also proteins modulated by downstream transcriptional responses, is still incompletely characterized and poorly understood. Earlier large-scale efforts to define the HSP90 proteome have been valuable but are incomplete because of limited technical sensitivity. Here, we discuss previous large-scale surveys of proteome perturbations induced by HSP90 inhibitors in light of a significant new study using state-of-the-art stable isotope labeling by amino acids (SILAC) technology combined with more sensitive highresolution mass spectrometry (MS) that extends the catalog of proteomic changes in inhibitor-treated cancer cells. Among wide-ranging changes, major functional responses include downregulation of protein kinase activity and the DNA damage response alongside upregulation of the protein degradation machinery. Despite this improved proteomic coverage, there was surprisingly little overlap with previous studies. This may be due in part to technical issues but is likely also due to the variability of the HSP90 proteome with the inhibitor conditions used, the cancer cell type and the genetic status of client proteins. We suggest future proteomic studies to address these factors, to help distinguish client protein components from indirect transcriptional

show abstract

Section: Introductionmentioning

confidence: 99%

The expanding proteome of the molecular chaperone HSP90

2012

View full text Add to dashboard Cite

show abstract

“…hsp90 stabilizes or activates numerous protein clients by binding to their unfolded, partly folded, or native-like forms (3,4). hsp90 functions as a homodimer, with each monomer consisting of a C-terminal dimerization domain (C), a middle domain (M) that is often involved in client binding, and an N-terminal domain (N) that contains the majority of the ATP-binding site and that participates in some client-binding interactions (5,6).…”

mentioning

confidence: 99%

Heat Shock Protein 90 Associates with the Per-Arnt-Sim Domain of Heme-free Soluble Guanylate Cyclase

Sarkar

Dai

Haque

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: hsp90␤ binds to heme-free sGC␤1 subunit to enable heme insertion during maturation, but the mechanism is unclear. Results: Their interaction involves the hsp90␤ M domain and the Per-Arnt-Sim (PAS) domain of apo-sGC␤1. Conclusion: hsp90␤ may modulate the apo-sGC␤1 through its PAS domain, suggesting a means to aid heme insertion. Significance: This work expands our knowledge of how hsp90 regulates PAS-containing client proteins like sGC.

show abstract

“…In this regard, the number of Hsp90 client proteins is nearly 400 proteins, a large number of them belonging to the proteinkinase family [44,[170][171][172]. Even so, a direct role of proteins such as FKBP51 and FKBP52 cannot be ruled out since these IMMs could also act per se in the subcellular distribution of nuclear factors in an Hsp90-independent manner.…”

Section: Discussionmentioning

confidence: 99%

The Emerging Role of TPR-Domain Immunophilins in the Mechanism of Action of Steroid Receptors

Mazaira

Lagadari

Erlejman

et al. 2014

Nuclear Receptor Research

View full text Add to dashboard Cite

Abstract. In the absence of ligand, some members of nuclear receptor family such as corticosteroid receptors are primarily located in the cytoplasm, and they rapidly accumulate in the nucleus upon ligand-binding. Other members of the family such as the estrogen receptor are mostly nuclear. Regardless of their primary location, these oligomeric proteins undergo a dynamic nuclearcytoplasmic shuttling, and their transport through the cytoplasmic compartment has always been assumed to occur in a stochastic manner by simple diffusion. Although heuristic, this oversimplified model has never been demonstrated. Moreover, it has always been assumed that the first step related to receptor activation is the dissociation of the Hsp90-based heterocomplex, a process referred to as 'transformation.' Nonetheless, recent experimental evidence indicates that the chaperone machinery is required for the retrotransport of the receptor throughout the cytoplasm and facilitates its active passage through the nuclear pore. Therefore, transformation is actually a nuclear event. A group of Hsp90-binding cochaperones belonging to the immunophilin family plays a cardinal role not only in the mechanism for receptor movement, but also in nuclear events leading to interactions with nuclear sites of action and the regulation of transcriptional activity. In this article we analyze the importance of molecular chaperones and TPR-domain immunophilins in the molecular mechanism of action of steroid receptors.

show abstract

The network interaction of the human cytosolic 90kDa heat shock protein Hsp90: A target for cancer therapeutics

Cited by 74 publications

References 185 publications

The expanding proteome of the molecular chaperone HSP90

The expanding proteome of the molecular chaperone HSP90

Heat Shock Protein 90 Associates with the Per-Arnt-Sim Domain of Heme-free Soluble Guanylate Cyclase

The Emerging Role of TPR-Domain Immunophilins in the Mechanism of Action of Steroid Receptors

Contact Info

Product

Resources

About