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https://www.readbyqxmd.com/read/29113312/fkbp51-decreases-cell-proliferation-and-increases-progestin-sensitivity-of-human-endometrial-adenocarcinomas-by-inhibiting-akt
#1
Jing Dong, Yulian Jiao, Wenli Mu, Bingru Lu, Muyun Wei, Linying Sun, Shengnan Hu, Bin Cui, Xiaowen Liu, Zijiang Chen, Yueran Zhao
In this study, we investigated the role of FK506 binding protein 51 (FKBP51) in human endometrial adenocarcinoma progression. Immunohistochemical analysis showed decreased FKBP51 expression in endometrial adenocarcinoma tissues. Moreover, higher FKBP51 expression was observed in the normal secretory phase than in proliferative-phase endometrial tissues. FKBP51-shRNA transfected KLE cells showed high Ser473-phospho Akt with decreased p21 and p27 levels, which promoted S-G2/M phase cell cycle progression and proliferation...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29079741/combined-x-ray-crystallography-and-computational-modeling-approach-to-investigate-the-hsp90-c-terminal-peptide-binding-to-fkbp51
#2
Rajnish Kumar, Martin Moche, Bengt Winblad, Pavel F Pavlov
FK506 binding protein of 51 kDa (FKBP51) is a heat shock protein 90 (Hsp90) co-chaperone involved in the regulation of steroid hormone receptors activity. It is known for its role in various regulatory pathways implicated in mood and stress-related disorders, cancer, obesity, Alzheimer's disease and corticosteroid resistant asthma. It consists of two FKBP12 like active peptidyl prolyl isomerase (PPIase) domains (an active FK1 and inactive FK2 domain) and one tetratricopeptide repeat (TPR) domain that mediates interaction with Hsp90 via its C-terminal MEEVD peptide...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29023988/molecular-dynamics-simulation-binding-free-energy-calculation-and-unbinding-pathway-analysis-on-selectivity-difference-between-fkbp51-and-fkbp52-insight-into-the-molecular-mechanism-of-isoform-selectivity
#3
Danfeng Shi, Qifeng Bai, Shuangyan Zhou, Xuewei Liu, Huanxiang Liu, Xiaojun Yao
As co-chaperones of the 90-kDa heat shock protein(HSP90), FK506 binding protein 51 (FKBP51) and FK506 binding protein 52 (FKBP52) modulate the maturation of steroid hormone receptor through their specific FK1 domains (FKBP12-like domain 1). The inhibitors targeting FK1 domains are potential therapies for endocrine-related physiological disorders. However, the structural conservation of the FK1 domains between FKBP51 and FKBP52 make it difficult to obtain satisfactory selectivity in FK506-based drug design. Fortunately, a series of iFit ligands synthesized by Hausch et al exhibited excellent selectivity for FKBP51, providing new opportunity for design selective inhibitors...
October 12, 2017: Proteins
https://www.readbyqxmd.com/read/28978117/a-regulatory-role-for-the-co-chaperone-fkbp51s-in-pd-l1-expression-in-glioma
#4
Paolo D'Arrigo, Michele Russo, Anna Rea, Martina Tufano, Elia Guadagno, Maria Laura Del Basso De Caro, Roberto Pacelli, Felix Hausch, Stefania Staibano, Gennaro Ilardi, Silvia Parisi, Maria Fiammetta Romano, Simona Romano
BACKGROUND: FKBP51 is a co-chaperone with isomerase activity, abundantly expressed in glioma. We previously identified a spliced isoform (FKBP51s) and highlighted a role for this protein in the upregulation of Programmed Death Ligand 1 (PD-L1) expression in melanoma. Because gliomas can express PD-L1 causing a defective host anti-tumoral immunity, we investigated whether FKBP51s was expressed in glioma and played a role in PD-L1 regulation in this tumour. METHODS: We used D54 and U251 glioblastoma cell lines that constitutively expressed PD-L1...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977697/expression-of-fk506-binding-protein-51-fkbp51-in-mycosis-fungoides
#5
M Mascolo, M F Romano, G Ilardi, S Romano, A Baldo, M Scalvenzi, G Argenziano, F Merolla, D Russo, S Varricchio, F Pagliuca, M Russo, G Ciancia, G De Rosa, S Staibano
BACKGROUND: Mycosis fungoides (MF) is the major subtype of cutaneous T-cell lymphomas (CTCL). It usually has a prolonged indolent clinical course with a minority of cases acquiring a more aggressive biological profile and resistance to conventional therapies, partially attributed to the persistent activation of Nuclear Factor-kappa B (NF-κB) pathway. In the last decade, several papers suggested an important role for the FK506-binding protein 51 (FKBP51), an immunophilin initially cloned in lymphocytes, in the control of NF-κB pathway in different types of human malignancies...
October 4, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28886589/role-of-fkbp51-in-the-modulation-of-the-expression-of-the-corticosteroid-receptors-in-bovine-thymus-following-glucocorticoid-administration
#6
L Starvaggi Cucuzza, B Biolatti, F E Scaglione, F T Cannizzo
The aim of this work was to study the transcriptional effects of glucocorticoids on corticosteroid hormone receptors, prereceptors (11β-hydroxysteroid dehydrogenase 1 and 2, 11β-HSD1 and 2), and chaperones molecules regulating intracellular trafficking of the receptors (FKBP51 and FKBP52) in thymus of veal calves. Moreover, the expression of FKBP51 and FKBP52 gene were investigated in beef cattle thymus. In the cervical thymus of veal calves, dexamethasone administration in combination with estradiol decreased FKBP51 expression (P < 0...
August 8, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28754882/a-regulatory-role-for-the-co-chaperone-fkbp51s-in-pd-l1-expression-in-glioma
#7
Paolo D'Arrigo, Michele Russo, Anna Rea, Martina Tufano, Elia Guadagno, Maria Laura Del Basso De Caro, Roberto Pacelli, Felix Hausch, Stefania Staibano, Gennaro Ilardi, Silvia Parisi, Maria Fiammetta Romano, Simona Romano
BACKGROUND: FKBP51 is a co-chaperone with isomerase activity, abundantly expressed in glioma. We previously identified a spliced isoform (FKBP51s) and highlighted a role for this protein in the upregulation of Programmed Death Ligand 1 (PD-L1) expression in melanoma. Because gliomas can express PD-L1 causing a defective host anti-tumoral immunity, we investigated whether FKBP51s was expressed in glioma and played a role in PD-L1 regulation in this tumour. METHODS: We used D54 and U251 glioblastoma cell lines that constitutively expressed PD-L1...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699905/fkbp51-decreases-cell-proliferation-and-increases-progestin-sensitivity-of-human-endometrial-adenocarcinomas-by-inhibiting-akt
#8
Jing Dong, Yulian Jiao, Wenli Mu, Bingru Lu, Muyun Wei, Linying Sun, Shengnan Hu, Bin Cui, Xiaowen Liu, Zijiang Chen, Yueran Zhao
In this study, we investigated the role of FK506 binding protein 51 (FKBP51) in human endometrial adenocarcinoma progression. Immunohistochemical analysis showed decreased FKBP51 expression in endometrial adenocarcinoma tissues. Moreover, higher FKBP51 expression was observed in the normal secretory phase than in proliferative-phase endometrial tissues. FKBP51-shRNA transfected KLE cells showed high Ser473-phospho Akt with decreased p21 and p27 levels, which promoted S-G2/M phase cell cycle progression and proliferation...
June 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28629826/silencing-of-fkbp51-alleviates-the-mechanical-pain-threshold-inhibits-drg-inflammatory-factors-and-pain-mediators-through-the-nf-kappab-signaling-pathway
#9
Hong-Mei Yu, Qi Wang, Wen-Bo Sun
Neuropathic pain is chronic pain caused by lesions or diseases of the somatosensory system, currently available analgesics provide only temporal relief. The precise role of FK506 binding protein 51 (FKBP51) in neuropathic pain induced by chronic constriction injury (CCI) is not clear. The purpose of the present study was to investigate the effects and possible mechanisms of FKBP51 in neuropathic pain in the rat model of CCI. Our results showed that FKBP51 was obviously upregulated in a time-dependent manner in the dorsal root ganglion (DRG) of CCI rats...
September 5, 2017: Gene
https://www.readbyqxmd.com/read/28524179/a-fkbp5-mutation-is-associated-with-paget-s-disease-of-bone-and-enhances-osteoclastogenesis
#10
Bingru Lu, Yulian Jiao, Yinchang Wang, Jing Dong, Muyun Wei, Bin Cui, Yafang Sun, Laicheng Wang, Bingchang Zhang, Zijiang Chen, Yueran Zhao
Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28493984/nasal-airway-epithelial-cell-il-6-and-fkbp51-gene-expression-and-steroid-sensitivity-in-asthmatic-children
#11
Michael Fayon, Aurelie Lacoste-Rodrigues, Pascal Barat, Jean-Christophe Helbling, Fabienne Nacka, Patrick Berger, Marie-Pierre Moisan, Jean-Benoit Corcuff
BACKGROUND: Many asthmatic patients exhibit uncontrolled asthma despite high-dose inhaled corticosteroids (ICS). Airway epithelial cells (AEC) have distinct activation profiles that can influence ICS response. OBJECTIVES: A pilot study to identify gene expression markers of AEC dysfunction and markers of corticosteroid sensitivity in asthmatic and non-asthmatic control children, for comparison with published reports in adults. METHODS: AEC were obtained by nasal brushings and primary submerged cultures, and incubated in control conditions or in the presence of 10 ng/ml TNFalpha, 10-8M dexamethasone, or both...
2017: PloS One
https://www.readbyqxmd.com/read/28441737/commitment-of-scaffold-proteins-in-the-onco-biology-of-human-colorectal-cancer-and-liver-metastases-after-oxaliplatin-based-chemotherapy
#12
Deborah Rotoli, Manuel Morales, Julio Ávila, María Del Carmen Maeso, María Del Pino García, Ali Mobasheri, Pablo Martín-Vasallo
Scaffold proteins play pivotal roles in the regulation of signaling pathways, integrating external and internal stimuli to various cellular outputs. We report the pattern of cellular and subcellular expression of scaffoldins angiomotin-like 2 (AmotL2), FK506 binding protein 5 (FKBP51) and IQ motif containing GTPase-activating protein 1 (IQGAP1) in colorectal cancer (CRC) and metastases in liver resected after oxaliplatin-based chemotherapy (CT). Positive immunostaining for the three scaffoldins was found in most cells in healthy colon, tumor, healthy liver and metastasized liver...
April 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28377614/the-hsp90-machinery-facilitates-the-transport-of-diphtheria-toxin-into-human-cells
#13
Manuel Schuster, Leonie Schnell, Peter Feigl, Carina Birkhofer, Katharina Mohr, Maurice Roeder, Stefan Carle, Simon Langer, Franziska Tippel, Johannes Buchner, Gunter Fischer, Felix Hausch, Manfred Frick, Carsten Schwan, Klaus Aktories, Cordelia Schiene-Fischer, Holger Barth
Diphtheria toxin kills human cells because it delivers its enzyme domain DTA into their cytosol where it inhibits protein synthesis. After receptor-mediated uptake of the toxin, DTA translocates from acidic endosomes into the cytosol, which might be assisted by host cell factors. Here we investigated the role of Hsp90 and its co-chaperones during the uptake of native diphtheria toxin into human cells and identified the components of the Hsp90 machinery including Hsp90, Hsp70, Cyp40 and the FK506 binding proteins FKBP51 and FKBP52 as DTA binding partners...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28363942/usp49-negatively-regulates-tumorigenesis-and-chemoresistance-through-fkbp51-akt-signaling
#14
Kuntian Luo, Yunhui Li, Yujiao Yin, Lei Li, Chenming Wu, Yuping Chen, Somaira Nowsheen, Qi Hu, Lizhi Zhang, Zhenkun Lou, Jian Yuan
The AKT pathway is a fundamental signaling pathway that mediates multiple cellular processes, such as cell proliferation and survival, angiogenesis, and glucose metabolism. We recently reported that the immunophilin FKBP51 is a scaffolding protein that can enhance PHLPP-AKT interaction and facilitate PHLPP-mediated dephosphorylation of AKT at Ser473, negatively regulating AKT activation. However, the regulation of FKBP51-PHLPP-AKT pathway remains unclear. Here we report that a deubiquitinase, USP49, is a new regulator of the AKT pathway...
May 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28283554/impaired-dual-specificity-protein-phosphatase-dusp4-reduces-corticosteroid-sensitivity
#15
Yoshiki Kobayashi, Kazuhiro Ito, Akira Kanda, Koich Tomoda, Nicolas Mercado, Peter J Barnes
We have reported that phosphorylation of the glucocorticoid receptor (GR) at Ser(226) reduces GR nuclear translocation, resulting in corticosteroid insensitivity in patients with severe asthmas. A serine/threonine protein phosphatase 2A, which regulates c-Jun N-terminal kinase (JNK) 1 and GR-Ser(226) signaling, is involved in this mechanism. Here, we further explored protein kinase dual-specificity phosphatases (DUSPs) with the ability to dephosphorylate JNK, and identified DUSP4 as a phosphatase involved in the regulation of corticosteroid sensitivity...
May 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28254433/loss-of-fkbp5-impedes-adipocyte-differentiation-under-both-normoxia-and-hypoxic-stress
#16
Lingling Zhang, Bin Qiu, Tingting Wang, Jun Wang, Ming Liu, Yuxue Xu, Chao Wang, Ran Deng, Kent Williams, Zhiwei Yang, Tiebing Liang, Weidong Yong
FK506-binding protein 51 (FKBP51) is one of the most important regulators in the GR-mediated stress response, and we previously demonstrated that loss of FKBP5 arrests adipogenesis and renders mice resistant to diet-induced obesity (DIO). However, the exact role of FKBP5 in the process of adipocyte differentiation under hypoxic conditions (the common microenvironment where adipocytes reside in obese individuals) is still unclear. Here, by isolating and culturing WT- and Fkbp5-knockout mouse embryonic fibroblasts (MEFs), and treat them at normal oxygen environment (21% O2, nomorxia) or low oxygen environment (5% O2, hypoxia)...
April 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28218707/fkbp51-immunohistochemical-expression-a-new-prognostic-biomarker-for-oscc
#17
Daniela Russo, Francesco Merolla, Massimo Mascolo, Gennaro Ilardi, Simona Romano, Silvia Varricchio, Virginia Napolitano, Angela Celetti, Loredana Postiglione, Pier Paolo Di Lorenzo, Luigi Califano, Giovanni Orabona Dell'Aversana, Fabio Astarita, Maria Fiammetta Romano, Stefania Staibano
Up-to-date, several molecular markers of prognosis have been studied in Oral Squamous Cell Carcinoma (OSCC), but none entered in the clinical setting. Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better stratify OSCC patients' risk to address targeted therapeutic strategies. The role of immune response in the pathogenesis and biological behavior of OSCC has been investigated by several authors, and promising results have been obtained with immune checkpoint inhibitors...
February 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28147277/regulation-of-serine-threonine-kinase-akt-activation-by-nad-dependent-deacetylase-sirt7
#18
Jia Yu, Bo Qin, Fengying Wu, Sisi Qin, Somaira Nowsheen, Shan Shan, Jacqueline Zayas, Huadong Pei, Zhenkun Lou, Liewei Wang
The Akt pathway is a central regulator that promotes cell survival in response to extracellular signals. Depletion of SIRT7, an NAD(+)-dependent deacetylase that is the least-studied sirtuin, is known to significantly increase Akt activity in mice through unknown mechanisms. In this study, we demonstrate that SIRT7 depletion in breast cancer cells results in Akt hyper-phosphorylation and increases cell survival following genotoxic stress. Mechanistically, SIRT7 specifically interacts with and deacetylates FKBP51 at residue lysines 28 and 155 (K28 and K155), resulting in enhanced interactions among FKBP51, Akt, and PHLPP, as well as Akt dephosphorylation...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28032931/fkbp51-regulates-cell-motility-and-invasion-via-rhoa-signaling
#19
Miho Takaoka, Shun Ito, Yoshio Miki, Akira Nakanishi
FK506 binding protein 51 (FKBP51), a member of the immunophilin family, is involved in multiple signaling pathways, tumorigenesis, and chemoresistance. FKBP51 expression correlates with metastatic potential in melanoma and prostate cancer. However, the functions of FKBP51, particularly involving the regulation of cell motility and invasion, are not fully understood. We discovered two novel interacting partner proteins of FKBP51, i.e., deleted in liver cancer 1 (DLC1) and deleted in liver cancer 2 (DLC2), using immunoprecipitation and mass spectrometry...
March 2017: Cancer Science
https://www.readbyqxmd.com/read/27844058/western-high-fat-diet-consumption-during-adolescence-increases-susceptibility-to-traumatic-stress-while-selectively-disrupting-hippocampal-and-ventricular-volumes
#20
Priya Kalyan-Masih, Julio David Vega-Torres, Christina Miles, Elizabeth Haddad, Sabrina Rainsbury, Mohsen Baghchechi, Andre Obenaus, Johnny D Figueroa
Psychological trauma and obesity co-occur frequently and have been identified as major risk factors for psychiatric disorders. Surprisingly, preclinical studies examining how obesity disrupts the ability of the brain to cope with psychological trauma are lacking. The objective of this study was to determine whether an obesogenic Western-like high-fat diet (WD) predisposes rats to post-traumatic stress responsivity. Adolescent Lewis rats (postnatal day 28) were fed ad libitum for 8 weeks with either the experimental WD diet (41...
September 2016: ENeuro
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