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Search results for: TCP1

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#34017352   2021/05/04 To Up

Chaperonin-Containing TCP1 Subunit 6A Is a Prognostic Potential Biomarker That Correlates With the Presence of Immune Infiltrates in Colorectal Cancer.

Chaperonin-containing TCP1 subunit (CCT) 6A is an oncogenic 6th subunit of the CCT family. Nevertheless, not much is documented regarding its function in colorectal cancer (COAD). This investigation seeks to explore the role of in the prognosis of COAD.
Hui Sun, Yan Wang, Hao-Yu Jing, Xin-Yu Yang, Xin-Xiu Shi, Jia-Hui Zhang, Yuan-Xiu Yu, Li Gao, Xin-Yue Wang, Wan-Hong Li, Lei Yu

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#33996588   2021/04/30 To Up

Chaperonin-Containing TCP1 Complex (CCT) Promotes Breast Cancer Growth Through Correlations With Key Cell Cycle Regulators.

Uncontrolled proliferation as a result of dysregulated cell cycling is one of the hallmarks of cancer. Therapeutically targeting pathways that control the cell cycle would improve patient outcomes. However, the development of drug resistance and a limited number of inhibitors that target multiple cell cycle modulators are challenges that impede stopping the deregulated growth that leads to malignancy. To advance the discovery of new druggable targets for cell cycle inhibition, we investigated the role of Chaperonin-Containing TCP1 (CCT or TRiC) in breast cancer cells. CCT, a type II chaperonin, is a multi-subunit protein-folding complex that interacts with many oncoproteins and mutant tumor suppressors. CCT subunits are highly expressed in a number of cancers, including breast cancer. We found that expression of one of the CCT subunits, CCT2, inversely correlates with breast cancer patient survival and is subject to copy number alterations through genomic amplification. To investigate a role for CCT2 in the regulation of the cell cycle, we expressed an exogenous CCT2-FLAG construct in T47D and MCF7 luminal A breast cancer cells and examined cell proliferation under conditions of two-dimensional (2D) monolayer and three-dimensional (3D) spheroid cultures. Exogenous CCT2 increased the proliferation of cancer cells, resulting in larger and multiple spheroids as compared to control cells. CCT2-expressing cells were also able to undergo spheroid growth reversal, re-attaching, and resuming growth in 2D cultures. Such cells gained anchorage-independent growth. CCT2 expression in cells correlated with increased expression of MYC, especially in spheroid cultures, and other cell cycle regulators like CCND1 and CDK2, indicative of a novel activity that could contribute to the increase in cell growth. Statistically significant correlations between CCT2, MYC, and CCND1 were shown. Since CCT2 is located on chromosome 12q15, an amplicon frequently found in soft tissue cancers as well as breast cancer, CCT2 may have the basic characteristics of an oncogene. Our findings suggest that CCT2 could be an essential driver of cell division that may be a node through which pathways involving MYC, cyclin D1 and other proliferative factors could converge. Hence the therapeutic inhibition of CCT2 may have the potential to achieve multi-target inhibition, overcoming the limitations associated with single agent inhibitors.
Heba Ghozlan, Adrian Showalter, Eunkyung Lee, Xiang Zhu, Annette R Khaled

2120 related Products with: Chaperonin-Containing TCP1 Complex (CCT) Promotes Breast Cancer Growth Through Correlations With Key Cell Cycle Regulators.

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#33940608   2021/05/03 To Up

Unraveling the impact of plant-density genetic architecture on agronomic traits in canola.

Plant density defines vegetative architecture and competition for light between individuals. Brassica napus (canola), as a model system of indeterminate growth, presents a radically different plant architecture compared to traditional crops commonly cultivated at high density. Using a panel of 152 spring-type canola accessions and a double haploid (DH) population of 99 lines from a cross between Lynx and Monty, we performed Genome-Wide-Analysis-Studies (GWAS) and Quantitative Trait Locus (QTL) mapping for 12 growth and yield traits at two contrasting plant densities (15 and 60 plants m -2). We revealed mostly novel associations by GWAS (19) and QTLs (11) for growth and yield traits being the most significant for flowering, biomass, rosette height, silique and seed number, and grain yield; often representing density-independent signals although we also uncovered some density-dependent associations typically mapping at low density. Further RNA-seq transcriptomics revealed distinctive latent gene regulatory responses to simulated shade between Lynx and Monty. Given the phylogenetic relatedness, we additionally used Arabidopsis thaliana aiming at testing genes to validate density effects of homologous counterparts mapping into relevant rapeseed QTLs. Our results suggest that TCP1 may promote the growth independently of plant neighbors, while HY5 could increase biomass and seed yield specifically at high plant density. For flowering time, the observations in tested mutants suggested that the corresponding genes may plausibly contribute to promote flowering in plant-density dependent (i.e., PIN) and independent (i.e., FT, HY5 and TCP1) manner. This work underscores the advantages of using agronomic field experiments together with genetic and transcriptomic approaches to decipher quantitative complex traits that potentially mediate superior crop productivity.
Yesica C Menendez, Diego H Sanchez, Rod J Snowdon, Deborah P Rondanini, Javier F Botto

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#33897772   2021/04/08 To Up

Prognostic Power of a Chaperonin Containing TCP-1 Subunit Genes Panel for Hepatocellular Carcinoma.

Chaperonin containing TCP-1 (T-complex protein 1) (CCT) is a large molecular weight complex that contains nine subunits (TCP1, CCT2, CCT3, CCT4, CCT5, CCT6A, CCT6B, CCT7, CCT8). This study aimed to reveal key genes which encode CCT subunits for prognosis and establish prognostic gene signatures based on CCT subunit genes. The data was downloaded from The Cancer Genome Atlas, International Cancer Genome Consortium and Gene Expression Omnibus. CCT subunit gene expression levels between tumor and normal tissues were compared. Corresponding Kaplan-Meier analysis displayed a distinct separation in the overall survival of CCT subunit genes. Correlation analysis, protein-protein interaction network, Gene Ontology analysis, immune cells infiltration analysis, and transcription factor network were performed. A nomogram was constructed for the prediction of prognosis. Based on multivariate Cox regression analysis and shrinkage and selection method for linear regression model, a three-gene signature comprising CCT4, CCT6A, and CCT6B was constructed in the training set and significantly associated with prognosis as an independent prognostic factor. The prognostic value of the signature was then validated in the validation and testing set. Nomogram including the signature showed some clinical benefit for overall survival prediction. In all, we built a novel three-gene signature and nomogram from CCT subunit genes to predict the prognosis of hepatocellular carcinoma, which may support the medical decision for HCC therapy.
Wenli Li, Jun Liu, Hetong Zhao

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#33869000   2021/04/02 To Up

Molecular and Clinical Characterization of CCT2 Expression and Prognosis Large-Scale Transcriptome Profile of Breast Cancer.

Molecular chaperones play important roles in regulating various cellular processes and malignant transformation. Expression of some subunits of molecular chaperone CCT/TRiC complex have been reported to be correlated with cancer development and patient survival. However, little is known about the expression and prognostic significance of Chaperonin Containing TCP1 Subunit 2 (CCT2). CCT2 is a gene encoding a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). Through the Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, we systematically reviewed a total of 2,994 cases with transcriptome data and analyzed the functional annotation of CCT2 by Gene ontology and KEGG analysis. Univariate and multivariate survival analysis were performed to investigate the prognostic value of CCT2 in breast cancer. We found CCT2 was significantly upregulated in various tumors. In breast cancer, CCT2 expression was significantly upregulated in HER2-positive (HER2+) group, and more malignant group. In addition, we investigated correlations between CCT2 and other CCT members. Interestingly, almost all CCTs expression were positively correlated with each other, but not CCT6B. Survival analysis suggested that CCT2 overexpression was independently associated with worse prognosis of patients with breast cancer, especially in luminal A subtype. In summary, our results revealed that CCT2 might be involved in regulating cell cycle pathway, and independently predicted worse prognosis in breast cancer patients. These findings may expand understanding of potential anti-CCT2 treatments. To our knowledge, this is the largest and most comprehensive study characterizing the expression pattern of CCT2 together with its prognostic values in breast cancer.
Qiang Liu, Yihang Qi, Xiangyi Kong, Xiangyu Wang, Wenxiang Zhang, Jie Zhai, Yazhe Yang, Yi Fang, Jing Wang

1186 related Products with: Molecular and Clinical Characterization of CCT2 Expression and Prognosis Large-Scale Transcriptome Profile of Breast Cancer.



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#33836586   // To Up

Structural and functional dissection of reovirus capsid folding and assembly by the prefoldin-TRiC/CCT chaperone network.

Intracellular protein homeostasis is maintained by a network of chaperones that function to fold proteins into their native conformation. The eukaryotic TRiC chaperonin (TCP1-ring complex, also called CCT for cytosolic chaperonin containing TCP1) facilitates folding of a subset of proteins with folding constraints such as complex topologies. To better understand the mechanism of TRiC folding, we investigated the biogenesis of an obligate TRiC substrate, the reovirus σ3 capsid protein. We discovered that the σ3 protein interacts with a network of chaperones, including TRiC and prefoldin. Using a combination of cryoelectron microscopy, cross-linking mass spectrometry, and biochemical approaches, we establish functions for TRiC and prefoldin in folding σ3 and promoting its assembly into higher-order oligomers. These studies illuminate the molecular dynamics of σ3 folding and establish a biological function for TRiC in virus assembly. In addition, our findings provide structural and functional insight into the mechanism by which TRiC and prefoldin participate in the assembly of protein complexes.
Jonathan J Knowlton, Daniel Gestaut, Boxue Ma, Gwen Taylor, Alpay Burak Seven, Alexander Leitner, Gregory J Wilson, Sreejesh Shanker, Nathan A Yates, B V Venkataram Prasad, Ruedi Aebersold, Wah Chiu, Judith Frydman, Terence S Dermody

1058 related Products with: Structural and functional dissection of reovirus capsid folding and assembly by the prefoldin-TRiC/CCT chaperone network.

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#33815471   2021/03/17 To Up

Systematic Characterization of Expression Profiles and Prognostic Values of the Eight Subunits of the Chaperonin TRiC in Breast Cancer.

Chaperonin-containing TCP-1 (TRiC or CCT) was demonstrated to be involved in oncogenesis of cancers carcinogenesis and development of various malignancies. Increasing experimental evidence indicated that dysregulation of TRiC was implicated in the tumor progression of breast cancer (BCa). However, few definitive studies have addressed the diverse expression patterns and prognostic values of eight TRiC subunits. Thus, we aimed to investigate the clinical significance of TRiC subunit expression and prognostic values for their possible implications in diagnosis and treatment of BCa.
Wen-Xiu Xu, Wei Song, Meng-Ping Jiang, Su-Jin Yang, Jian Zhang, Dan-Dan Wang, Jin-Hai Tang

2146 related Products with: Systematic Characterization of Expression Profiles and Prognostic Values of the Eight Subunits of the Chaperonin TRiC in Breast Cancer.



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#33756344   2021/03/20 To Up

Arabidopsis SMAX1 overaccumulation suppresses rosette shoot branching and promotes leaf and petiole elongation.

SMAX1/SMXL (SUPPRESSOR OF MAX2 1/SMAX1-LIKE) proteins function as transcriptional repressors in karrikin and strigolactone (SL) signaling pathways and regulate plant architecture. MAX2 is a common factor in the two signaling pathways and a component of the SCF complex that modulates the proteasome-mediated degradation of SMAX1/SMXLs. SMXL6, 7, and 8 proteins promote shoot branching and inhibit petiole elongation. Our study found that the accumulation of SMAX1 suppresses rosette shoot branching and increases cauline branches on the primary inflorescence stem, plant height, petiole length, and leaf length/width ratio. The SMAX1 accumulation enhances the expression of BRC1, HB53, HB40, and HB21 that modulate shoot branching. SMAX1 also regulates the expression of the genes involved in auxin transport, cytokinin signaling pathway, and SL biosynthesis. The expression analyses of these genes suggest that excessive SMAX1 should accelerate the transport of auxin and the biosynthesis of SL in plants. High SL concentration suppresses the bud development in smax1D mutant that accumulates SMAX1 protein in plant. However, the effects of cytokinin and auxin on shoot branching remain elusive in the mutant with excessive SMAX1. SMAX1 regulates leaf shape and petiole length via modulating TCP1 expression. Our findings reveal a novel function of SMAX1 and new mechanism of shoot branching.
Xiujuan Zheng, Xianfeng Yang, Zheng Chen, Wenjia Xie, Xinwu Yue, Haipeng Zhu, Sique Chen, Xinli Sun

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#33736277   2020/10/22 To Up

Leishmania donovani chaperonin TCP1γ subunit protects miltefosine induced oxidative damage.

T-complex protein-1 (TCP1) is a chaperonin protein known to fold various proteins like actin and tubulin. In Leishmania donovani only one subunit of TCP1 that is gamma subunit (LdTCP1γ) has been functionally characterized. It not only performs ATP dependent protein folding but is also essential for survival and virulence. The present work demonstrates that LdTCP1γ also has a role in miltefosine resistance. Overexpression of LdTCP1γ in L. donovani promastigotes results in decreased sensitivity of parasites towards miltefosine, while single-allele replacement mutants exhibited increased sensitivity as compared to wild-type promastigotes. This response was specific to miltefosine with no cross-resistance to other drugs. The LdTCP1γ-mediated drug resistance was directly related to miltefosine-induced apoptotic death of the parasite, as was evidenced by 2 to 3-fold decrease in cell death parameters in overexpressing cells and >2-fold increase in single-allele replacement mutants. Further, deciphering the mechanism revealed that resistance of overexpressing cells was associated with efficient ROS neutralization due to increased levels of thiols and upregulation of cytosolic tryparedoxin peroxidase (cTxnPx). Further, modulation of LdTCP1γ expression in parasite also modulates the levels of proinflammatory cytokine (TNF-α) and anti-inflammatory cytokine (IL-10) of the host macrophages. The study provides evidence for the involvement of a chaperonin protein LdTCP1γ in the protection against miltefosine induced oxidative damage and reveals the fundamental role of LdTCP1γ in parasite biology.
Shailendra Yadav, Vahab Ali, Yatendra Singh, Sanjeev Kanojia, Neena Goyal

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#33610917   2021/02/18 To Up

WDR35 is involved in subcellular localization of acetylated tubulin in 293T cells.

WDR35/IFT121 is an intraflagellar transport protein in primary cilia, which is associated with RagA, an mTORC1-activating protein. To elucidate the functions of the interaction between WDR35 and RagA in primary cilia, as well as mTOR signaling, we identified WDR35-interacting proteins using mass spectrometry. We found that WDR35 associates with CCT complex proteins including TCP1/CCT1, which act as molecular chaperones for α-tubulin folding. Immunostaining showed that acetylated α-tubulin was concentrated in the vicinity of primary cilia in 293T cells. In contrast, acetylated tubulin was dispersed in WDR35 partial knockout cells established from 293T cells. Similarly, scattered subcellular localization of acetylated tubulin was observed in RagA knockout cells. RagA was present in the primary cilia of NIH3T3 cells, and the GDP form of RagA exhibited strong binding to WDR35 and negative regulation of primary cilium formation. These results suggest that WDR35 is involved in the subcellular localization of acetylated tubulin in primary cilia via its interactions with TCP1 and/or RagA family proteins.
Takeshi Sekiguchi, Takashi Ishii, Hideki Kobayashi, Nobuaki Furuno

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