Shape changes induced by N-terminal platination of ubiquitin by cisplatin

Williams, Jonathan P.; Phillips, Hazel I. A.; Campuzano, Iain; Sadler, Peter J.

doi:10.1016/j.jasms.2010.02.012

Cited by 50 publications

(47 citation statements)

References 41 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result is considered a signal of the damage of the ubiquitin-proteasome system induced by cisplatin, which may also be an important reason for the accumulation of improperly folded proteins and severe ER stress. Williams et al [2010] demonstrated that cisplatin combines directly with ubiquitin and changes its conformation, which may be the underlying mechanism explaining our result.…”

Section: Discussionsupporting

confidence: 56%

Endoplasmic Reticulum Stress Is Involved in Cochlear Cell Apoptosis in a Cisplatin-Induced Ototoxicity Rat Model

Zong¹,

Liu²,

Wan³

et al. 2017

Audiol Neurotol

View full text Add to dashboard Cite

Endoplasmic reticulum (ER) stress arises when excessive improperly folded proteins accumulate in the ER lumen. When ER stress occurs, the unfolded protein response (UPR) is subsequently activated to restore ER proteostasis. However, severe ER stress leads to apoptosis. Recent studies have suggested that cisplatin cytotoxicity may be related to ER stress. The purpose of this study was to determine whether ER stress participates in cochlear cell apoptosis in a cisplatin-induced ototoxicity rat model and to also determine the possible relationship between ER stress and hearing loss. Our results revealed that treatment with cisplatin upregulated the expression of active caspase-12 in cochlear cells, which is indicative of cisplatin-induced activation of ER-specific apoptosis. Increased expression of C/EBP homologous protein (CHOP) and cleaved caspase-9 suggested a close relationship between severe ER stress and mitochondria-dependent apoptosis in the cochlear cells of cisplatin-treated rats. In addition, we found that tauroursodeoxycholic acid (TUDCA), a promoter of ER proteostasis, had a protective effect on cisplatin-induced hearing loss. These results demonstrate that ER stress is involved in the cisplatin-induced apoptosis of cochlear cells in vivo.

show abstract

Section: Discussionsupporting

confidence: 56%

Endoplasmic Reticulum Stress Is Involved in Cochlear Cell Apoptosis in a Cisplatin-Induced Ototoxicity Rat Model

Zong¹,

Liu²,

Wan³

et al. 2017

Audiol Neurotol

View full text Add to dashboard Cite

show abstract

“…Thep resence of multiple conformers can also be inferred from the initial 31 PNMR spectra where two distinct 31 PNMR peaks indicate at least two different environments for the P( and hence Au)a toms ( Figure S6). [19,20] Ruthenium(II)peptide interactions studied by IM highlight the important role played by the ligand in determining the shape of the adduct formed. [3][4][17][18] Ion mobility has been used to study changes in the tertiary structure of ubiquitin upon metalation with cisplatin and revealed the presence of up to three different conformations for the Ub-{Pt(NH 3 ) 2 }m onoadduct.…”

Section: Zuschriftenmentioning

confidence: 99%

Diversity in Gold Finger Structure Elucidated by Traveling‐Wave Ion Mobility Mass Spectrometry

Paiva

Nelson

et al. 2017

Angew Chem Int Ed

View full text Add to dashboard Cite

Traveling wave ion mobility (TWIM) mass spectrometry (MS) is a powerful method for the structural and conformational analysis of proteins and peptides, enabling the differentiation of isomeric peptides (or proteins) that have the same sequence but are modified at different residues. In this study, the TWIM-MS technique was used to separate isomeric Au metallopeptide ions that were formed by Zn displacement from the parent zinc fingers (ZFs). The synthetic gold finger peptides were derived from the C-terminus of the HIV nucleocapsid p7 protein (NCp7-F2) and finger 3 of the Sp1 transcription factor (Sp1-F3). TWIM-MS enabled the acquisition of distinct product ion spectra for each isomer, clearly indicating the binding sites for the major conformers in the presence of multiple coordination possibilities. Collision cross-section measurements showed that the aurated peptide has a slightly more compact structure than the parent zinc compound NCp7-F2, which showed only one conformation.

show abstract

“…Platinum has been reported to bind to several proteins, including ubiquitin, Hsp90, G-actin, and other cytoskeletal proteins (2,(20)(21)(22)(23). For some of these, the binding resulted in conformational changes and subsequent altered biologic function (21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Molecular Pathways: The Immunogenic Effects of Platinum-Based Chemotherapeutics

Hato

Khong

Vries

et al. 2014

Clinical Cancer Research

376

286

View full text Add to dashboard Cite

The platinum-based drugs cisplatin, carboplatin, and oxaliplatin belong to the most widely used chemotherapeutics in oncology, showing clinical efficacy against many solid tumors. Their main mechanism of action is believed to be the induction of cancer cell apoptosis as a response to their covalent binding to DNA. In recent years, this picture has increased in complexity, based on studies indicating that cellular molecules other than DNA may potentially act as targets, and that part of the antitumor effects of platinum drugs occurs through modulation of the immune system. These immunogenic effects include modulation of STAT signaling; induction of an immunogenic type of cancer cell death through exposure of calreticulin and release of ATP and high-mobility group protein box-1 (HMGB-1); and enhancement of the effector immune response through modulation of programmed death receptor 1-ligand and mannose-6-phosphate receptor expression. Both basic and clinical studies indicate that at least part of the antitumor efficacy of platinum chemotherapeutics may be due to immune potentiating mechanisms. Clinical studies exploiting this novel mechanism of action of these old cancer drugs have been initiated. Here, we review the literature on the immunogenic effects of platinum, summarize the clinical advances using platinum as a cytotoxic compound with immune adjuvant properties, and discuss the limitations to these studies and the gaps in our understanding of the immunologic effects of these drugs.

show abstract

Shape changes induced by N-terminal platination of ubiquitin by cisplatin

Cited by 50 publications

References 41 publications

Endoplasmic Reticulum Stress Is Involved in Cochlear Cell Apoptosis in a Cisplatin-Induced Ototoxicity Rat Model

Endoplasmic Reticulum Stress Is Involved in Cochlear Cell Apoptosis in a Cisplatin-Induced Ototoxicity Rat Model

Diversity in Gold Finger Structure Elucidated by Traveling‐Wave Ion Mobility Mass Spectrometry

Molecular Pathways: The Immunogenic Effects of Platinum-Based Chemotherapeutics

Contact Info

Product

Resources

About