Structural basis for the regulatory role of the PPxY motifs in the thioredoxin-interacting protein TXNIP

2016 ◽  
Vol 473 (2) ◽  
pp. 179-187 ◽  
Author(s):  
Yanli Liu ◽  
Johnathan Lau ◽  
Weiguo Li ◽  
Wolfram Tempel ◽  
Li Li ◽  
...  
Keyword(s):  
Regulatory Role ◽  
Structural Basis ◽  
Structural Studies ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Multivalent Interactions

Itch binds directly to and negatively regulates TXNIP. Structural studies revealed the regulatory role of the PPxY motifs in TXNIP: TNXIP binds to Itch through multivalent interactions, whereas phosphorylation of TNXIP switched its binding to SHP2.

scholarly journals Role of Thioredoxin-Interacting Protein in Diseases and Its Therapeutic Outlook

2021 ◽  
Vol 22 (5) ◽  
pp. 2754
Author(s):  
Naila Qayyum ◽  
Muhammad Haseeb ◽  
Moon Suk Kim ◽  
Sangdun Choi
Keyword(s):  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Signaling Complex ◽  
Current Review ◽  
Wide Range ◽  
Range Of Functions ◽  
Species Production ◽  
And Oxidative Stress ◽  
Significant Attention

Thioredoxin-interacting protein (TXNIP), widely known as thioredoxin-binding protein 2 (TBP2), is a major binding mediator in the thioredoxin (TXN) antioxidant system, which involves a reduction-oxidation (redox) signaling complex and is pivotal for the pathophysiology of some diseases. TXNIP increases reactive oxygen species production and oxidative stress and thereby contributes to apoptosis. Recent studies indicate an evolving role of TXNIP in the pathogenesis of complex diseases such as metabolic disorders, neurological disorders, and inflammatory illnesses. In addition, TXNIP has gained significant attention due to its wide range of functions in energy metabolism, insulin sensitivity, improved insulin secretion, and also in the regulation of glucose and tumor suppressor activities in various cancers. This review aims to highlight the roles of TXNIP in the field of diabetology, neurodegenerative diseases, and inflammation. TXNIP is found to be a promising novel therapeutic target in the current review, not only in the aforementioned diseases but also in prolonged microvascular and macrovascular diseases. Therefore, TXNIP inhibitors hold promise for preventing the growing incidence of complications in relevant diseases.

scholarly journals Endothelial pro-atherosclerotic response to extracellular diabetic-like environment: Possible role of thioredoxin-interacting protein

2010 ◽  
Vol 25 (7) ◽  
pp. 2141-2149 ◽  
Author(s):  
T. Zitman-Gal ◽  
J. Green ◽  
M. Pasmanik-Chor ◽  
V. Oron-Karni ◽  
J. Bernheim
Keyword(s):  
Interacting Protein ◽  
Thioredoxin Interacting Protein

scholarly journals Plasticity at the DNA recognition site of the MeCP2 mCG-binding domain

2019 ◽  
Author(s):  
Ming Lei ◽  
Wolfram Tempel ◽  
Ke Liu ◽  
Jinrong Min
Keyword(s):  
Crystal Structures ◽  
Transcriptional Repression ◽  
Consensus Sequence ◽  
Complex Structure ◽  
Structural Basis ◽  
Structural Studies ◽  
Transcription Activator ◽  
Methylated Dna ◽  
Attachment Region

AbstractMeCP2 is an abundant protein, involved in transcriptional repression by binding to CG and non-CG methylated DNA. However, MeCP2 might also function as a transcription activator as MeCP2 is found bound to sparsely methylated promoters of actively expressed genes. Furthermore, Attachment Region Binding Protein (ARBP), the chicken ortholog of MeCP2, has been reported to bind to Matrix/scaffold attachment regions (MARs/SARs) DNA with an unmethylated 5’-CAC/GTG-3’ consensus sequence. In this study, we investigated how MeCP2 recognizes unmethylated 5’-CAC/GTG-3’ motif containing DNA by binding and structural studies. We found that MeCP2-MBD binds to MARs DNA with a comparable binding affinity to mCG DNA, and the MeCP2-CAC/GTG complex structure revealed that MeCP2 residues R111 and R133 form base-specific interactions with the GTG motif. For comparison, we also determined crystal structures of the MeCP2-MBD bound to mCG and mCAC/GTG DNA, respectively. Together, these crystal structures illustrate the adaptability of the MeCP2-MBD toward the GTG motif as well as the mCG DNA, and also provide structural basis of a biological role of MeCP2 as a transcription activator and its disease implications in Rett syndrome.

Long non-coding RNA MEG3 silencing and microRNA-214 restoration elevate osteoprotegerin expression to ameliorate osteoporosis by limiting TXNIP

2019 ◽  
Author(s):  
Rui Ding ◽  
ZhengTao Gu ◽  
ChangSheng Yang ◽  
CaiQiang Huang ◽  
QingChu Li ◽  
...  
Keyword(s):  
Interacting Protein ◽  
Blood Samples ◽  
Rat Models ◽  
Thioredoxin Interacting Protein ◽  
Non Coding Rna ◽  
Proliferation And Differentiation ◽  
Non Coding Rnas ◽  
Long Non Coding Rna ◽  
Rat Osteoblasts

Abstract BackgroundLong non-coding RNAs (LncRNAs) have been found to regulate innumerable diseases, yet the role of lncRNA MEG3 in osteoporosis (OP) has rarely been discussed. Here, we intend to probe into the mechanism of MEG3 on OP development by modulating microRNA-214 (miR-214) and thioredoxin-interacting protein (TXNIP)MethodsRat models of OP were established. MEG3, miR-214, and TXNIP mRNA expression in rat femoral tissues was detected, along with TXNIP, PCNA, cyclin D1, OCN, RUNX2, Osteolix, OPG, and PANKL protein expression. Ca, P and ALP contents in rat blood samples were also determined. Primary osteoblasts were isolated and cultured. Viability, COL-I, COL-II and COL-Χ contents, ALP content and activity, and mineralized nodule area of rat osteoblasts in each group were further detected.ResultsMEG3 and TXNIP were overexpressed while miR-214 was underexpressed in femoral tissues of OP rats. MEG3 silencing and miR-214 overexpression increased BMD, BV/TV, Tb.N, Tb.Th, the number of osteoblasts, collagen area and OPG expression, and downregulated PANKL of femoral tissues in OP rats. MEG3 silencing and miR-214 overexpression elevated Ca and P contents and reduced ALP content in OP rats’ blood, elevated viability, differentiation ability, COL-I and COL-Χ contents and ALP activity, and abated COL-II content of osteoblasts. MEG3 specifically bound to miR-214 to regulate TXNIP.ConclusionCollectively, we demonstrated that MEG3 silencing and miR-214 overexpression promote proliferation and differentiation of osteoblasts in OP by downregulating TXNIP, which further improves OP.

scholarly journals Role of thioredoxin-interacting protein in mediating endothelial dysfunction in hypertension

2020 ◽  
Author(s):  
Ruiyu Wang ◽  
Yongzheng Guo ◽  
Lingjiao Li ◽  
Minghao Luo ◽  
Linqian Peng ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

scholarly journals The Emerging Role of TXNIP in Ischemic and Cardiovascular Diseases; A Novel Marker and Therapeutic Target

2021 ◽  
Vol 22 (4) ◽  
pp. 1693
Author(s):  
Alison Domingues ◽  
Julia Jolibois ◽  
Perrine Marquet de Rougé ◽  
Valérie Nivet-Antoine
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Therapeutic Target ◽  
Redox Status ◽  
Interacting Protein ◽  
Cellular Redox ◽  
Thioredoxin Interacting Protein ◽  
Potential Biomarker ◽  
Ischemic Diseases

Thioredoxin interacting protein (TXNIP) is a metabolism- oxidative- and inflammation-related marker induced in cardiovascular diseases and is believed to represent a possible link between metabolism and cellular redox status. TXNIP is a potential biomarker in cardiovascular and ischemic diseases but also a novel identified target for preventive and curative medicine. The goal of this review is to focus on the novelties concerning TXNIP. After an overview in TXNIP involvement in oxidative stress, inflammation and metabolism, the remainder of this review presents the clues used to define TXNIP as a new marker at the genetic, blood, or ischemic site level in the context of cardiovascular and ischemic diseases.

scholarly journals The Role of Xgrip210 in γ-Tubulin Ring Complex Assembly and Centrosome Recruitment

2000 ◽  
Vol 151 (7) ◽  
pp. 1525-1536 ◽  
Author(s):  
Lijun Zhang ◽  
Thomas J. Keating ◽  
Andrew Wilde ◽  
Gary G. Borisy ◽  
Yixian Zheng
Keyword(s):  
Immunogold Labeling ◽  
Structural Studies ◽  
Complex Assembly ◽  
Interacting Protein ◽  
Centrosomal Protein ◽  
Ring Complex

The γ-tubulin ring complex (γTuRC), purified from the cytoplasm of vertebrate and invertebrate cells, is a microtubule nucleator in vitro. Structural studies have shown that γTuRC is a structure shaped like a lock-washer and topped with a cap. Microtubules are thought to nucleate from the uncapped side of the γTuRC. Consequently, the cap structure of the γTuRC is distal to the base of the microtubules, giving the end of the microtubule the shape of a pointed cap. Here, we report the cloning and characterization of a new subunit of Xenopus γTuRC, Xgrip210. We show that Xgrip210 is a conserved centrosomal protein that is essential for the formation of γTuRC. Using immunogold labeling, we found that Xgrip210 is localized to the ends of microtubules nucleated by the γTuRC and that its localization is more distal, toward the tip of the γTuRC-cap structure, than that of γ-tubulin. Immunodepletion of Xgrip210 blocks not only the assembly of the γTuRC, but also the recruitment of γ-tubulin and its interacting protein, Xgrip109, to the centrosome. These results suggest that Xgrip210 is a component of the γTuRC cap structure that is required for the assembly of the γTuRC.

scholarly journals The structural basis for the negative regulation of thioredoxin by thioredoxin-interacting protein

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Jungwon Hwang ◽  
Hyun-Woo Suh ◽  
Young Ho Jeon ◽  
Eunha Hwang ◽  
Loi T. Nguyen ◽  
...  
Keyword(s):  
Negative Regulation ◽  
Structural Basis ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

scholarly journals Expression and Regulatory Role of GAIP-Interacting Protein GIPC in Pancreatic Adenocarcinoma

2006 ◽  
Vol 66 (21) ◽  
pp. 10264-10268 ◽  
Author(s):  
Michael H. Muders ◽  
Shamit K. Dutta ◽  
Ling Wang ◽  
Julie S. Lau ◽  
Resham Bhattacharya ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Regulatory Role ◽  
Interacting Protein
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