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https://www.readbyqxmd.com/read/28904211/zonda-is-a-novel-early-component-of-the-autophagy-pathway-in-drosophila
#1
Mariana Melani, Ayelén Valko, Nuria M Romero, Milton O Aguilera, Julieta M Acevedo, Zambarlal Bhujabal, Joel Perez-Perri, Rocío V de la Riva-Carrasco, Maximiliano J Katz, Eleonora Sorianello, Cecilia D'Alessio, Gabor Juhász, Terje Johansen, María I Colombo, Pablo Wappner
Autophagy is an evolutionary conserved process by which eukaryotic cells undergo self-digestion of cytoplasmic components. Here we report that a novel Drosophila immunophilin, which we have named Zonda, is critically required for starvation-induced autophagy. We show that Zonda operates at early stages of the process, specifically for Vps34-mediated phosphatidylinositol 3-phosphate (PI3P) deposition. Zonda displays an even distribution under basal conditions, and soon after starvation nucleates in endoplasmic reticulum-associated foci that colocalize with omegasome markers...
September 13, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28864813/the-immunophilin-fkbp12-inhibits-hepcidin-expression-by-binding-the-bmp-type-i-receptor-alk2-in-hepatocytes
#2
Silvia Colucci, Alessia Pagani, Mariateresa Pettinato, Irene Artuso, Antonella Nai, Clara Camaschella, Laura Silvestri
The expression of the key regulator of iron homeostasis hepcidin is activated by the BMP-SMAD pathway in response to iron and inflammation and among drugs, by rapamycin, which inhibits mTOR in complex with the immunophilin FKBP12. FKBP12 interacts with BMP type I receptors to avoid uncontrolled signaling. By pharmacologic and genetic studies we identify FKBP12 as a novel hepcidin regulator. Sequestration of FKBP12 by rapamycin or tacrolimus activates hepcidin both in vitro and in murine hepatocytes. Acute tacrolimus treatment transiently increases hepcidin in wild type mice...
September 1, 2017: Blood
https://www.readbyqxmd.com/read/28852180/pathway-based-expression-profiling-of-benign-prostatic-hyperplasia-and-prostate-cancer-delineates-an-immunophilin-molecule-associated-with-cancer-progression
#3
Ankur Bhowal, Subhadipa Majumder, Subarna Ghosh, Sanmitra Basu, Debrup Sen, Susanta Roychowdhury, Sanghamitra Sengupta, Urmi Chatterji
Aberrant restoration of AR activity is linked with prostate tumor growth, therapeutic failures and development of castrate-resistant prostate cancer. Understanding the processes leading to AR-reactivation should provide the foundation for novel avenues of drug discovery. A differential gene expression study was conducted using biopsies from CaP and BPH patients to identify the components putatively responsible for reinstating AR activity in CaP. From the set of genes upregulated in CaP, FKBP52, an AR co-chaperone, was selected for further analysis...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820434/neuroprotective-and-nerve-regenerative-approaches-for-treatment-of-erectile-dysfunction-after-cavernous-nerve-injury
#4
REVIEW
Jeffrey D Campbell, Arthur L Burnett
Erectile dysfunction (ED) is a significant cause of reduced quality of life in men and their partners. Cavernous nerve injury (CNI) during pelvic surgery results in ED in greater than 50% of patients, regardless of additional patient factors. ED related to CNI is difficult to treat and typically poorly responsive to first- and second-line therapeutic options. Recently, a significant amount of research has been devoted to exploring neuroprotective and neuroregenerative approaches to salvage erectile function in patients with CNI...
August 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28767697/cyclophilin-a-potentiates-trim5%C3%AE-inhibition-of-hiv-1-nuclear-import-without-promoting-trim5%C3%AE-binding-to-the-viral-capsid
#5
Mallori Burse, Jiong Shi, Christopher Aiken
The host immunophilin cyclophilin A (CypA) binds to the capsid protein (CA) of HIV-1 and regulates its infectivity. Depending on the target cell type, CypA can either promote or inhibit HIV-1 infection. The ability of CypA to promote HIV-1 infection has been extensively studied and linked to several steps in early replication including uncoating, reverse transcription and nuclear import. By contrast, the mechanism by which CypA inhibits infection is less well understood. We investigated the mechanism by which CypA potentiates restriction of HIV-1 by the tripartite motif-containing protein 5 (TRIM5α)...
2017: PloS One
https://www.readbyqxmd.com/read/28760196/effects-of-pep-1-fk506bp-on-cyst-formation-in-polycystic-kidney-disease
#6
Hyo Sang Jo, Won Sik Eum, Eun Young Park, Je Young Ko, Do Yeon Kim, Dae Won Kim, Min Jea Shin, Ora Son, Su Bin Cho, Jung Hwan Park, Chi Hern Lee, Eun Ji Yeo, Hyeon Ji Yeo, Yeon Joo Choi, Jong Kyu Youn, Sung-Woo Cho, Jinseu Park, Jong Hoon Park, Soo Young Choi
Polycystic kidney disease (PKD) is one of the most common inherited disorders, whereby progressive cyst formation in the kidney leads to renal failure. FK506 binding protein 12 (FK506BP) is an immunophilin protein which performs multiple functions including regulation of cell signaling and survival. In this study, we determined the roles of PEP-1-FK506BP on cell proliferation and cyst formation in PKD cells. Purified PEP-1-FK506BP transduced into PKD cells and markedly inhibited cell proliferation. Also, PEP-1-FK506BP drastically inhibited the expression levels of p-Akt, p-p70S6K, p-mTOR, and p-ERK in PKD cells...
July 28, 2017: BMB Reports
https://www.readbyqxmd.com/read/28731139/inhibitory-effects-of-fkbp14-on-human-cervical-cancer-cells
#7
Lian-Yi Sun, Jiu-Zhi Tao, Bing Yan, Jian-Shu Lin
The FK506-binding protein 14 (FKBP14), which belongs to a subfamily of immunophilins, has been implicated in various biochemical processes. However, its effects on human cervical cancer remain to be elucidated. The present study aimed to determine the exact role of FKBP14 in human cervical cancer cell proliferation, cell cycle progression, apoptosis, invasion and migration. Cell proliferation was measured by Cell Counting Kit‑8 assay. Flow cytometry was conducted to determine the effects of FKBP14 on cell cycle progression and apoptosis...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28689771/immunosuppression-with-tacrolimus-improved-implantation-and-rescued-expression-of-uterine-progesterone-receptor-and-its-co-regulators-fkbp52-and-piasy-at-nidation-in-the-obese-and-diabetic-mice-comparative-studies-with-metformin
#8
Ahmad J H Albaghdadi, Frederick W K Kan
Diabesity is often associated with subfertility and recurrent miscarriages. Evidence links systemic and local uterine cytotoxicity to the pathogenesis of implantation failure (IF) in diabetes. Immunosuppression with tacrolimus improved pregnancy outcomes in obese and diabetic mice and repeated IF in women with elevated Th1/Th2 blood cell ratios. However the mode of action of tacrolimus in protecting against IF and the molecular mechanisms associated with recurrent miscarriages in the obese and diabetic subjects are yet to be elucidated...
July 6, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28643580/cyclophilins-less-studied-proteins-with-critical-roles-in-pathogenesis
#9
Khushwant Singh, Mark Winter, Miloslav Zouhar, Pavel Rysanek
Cyclophilins (EC 5.2.1.8) (CYPs) belong to a subgroup of proteins known as immunophilins, which also include FK-506 binding proteins (FKBPs) and parvulins. Members of the immunophilins have two main characteristic properties: I) peptidyl-prolyl cis-trans isomerase activity (PPIases) and II) the ability to bind immunosuppressant molecules of fungal origin. Cyclophilins are some of the most conserved proteins present in eukaryotes and prokaryotes, and they have been implicated in diverse cellular processes and responses to multiple biotic and abiotic stresses...
June 23, 2017: Phytopathology
https://www.readbyqxmd.com/read/28567569/on-the-role-ecology-phylogeny-and-structure-of-dual-family-immunophilins
#10
Sailen Barik
The novel class of dual-family immunophilins (henceforth abbreviated as DFI) represents naturally occurring chimera of classical FK506-binding protein (FKBP) and cyclophilin (CYN), connected by a flexible linker that may include a three-unit tetratricopeptide (TPR) repeat. Here, I report a comprehensive analysis of all current DFI sequences and their host organisms. DFIs are of two kinds: CFBP (cyclosporin- and FK506-binding protein) and FCBP (FK506- and cyclosporin-binding protein), found in eukaryotes. The CFBP type occurs in select bacteria that are mostly extremophiles, such as psychrophilic, thermophilic, halophilic, and sulfur-reducing...
May 31, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28363942/usp49-negatively-regulates-tumorigenesis-and-chemoresistance-through-fkbp51-akt-signaling
#11
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/28218707/fkbp51-immunohistochemical-expression-a-new-prognostic-biomarker-for-oscc
#12
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/28074922/soybean-cyclophilin-gmcyp1-interacts-with-an-isoflavonoid-regulator-gmmyb176
#13
Hemanta Raj Mainali, Arun Kumaran Anguraj Vadivel, Xuyan Li, Mark Gijzen, Sangeeta Dhaubhadel
Cyclophilins (CYPs) belong to the immunophilin superfamily with peptidyl-prolyl cis-trans isomerase (PPIase) activity. They catalyze the interconversion of the cis- and trans-rotamers of the peptidyl-prolyl amide bond of peptides. A yeast-two-hybrid screening using the isoflavonoid regulator GmMYB176 as bait identified GmCYP1 as one of the interacting proteins in soybean embryos. GmCYP1 localizes both in the nucleus and cytoplasm, and interacts in planta with GmMYB176, in the nucleus, and with SGF14l (a soybean 14-3-3 protein) in the nucleus and the cytoplasm...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28032931/fkbp51-regulates-cell-motility-and-invasion-via-rhoa-signaling
#14
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/27734179/quantifying-protein-dynamics-in-the-ps-ns-time-regime-by-nmr-relaxation
#15
Griselda Hernández, David M LeMaster
Both (15)N chemical shift anisotropy (CSA) and sufficiently rapid exchange linebroadening transitions exhibit relaxation contributions that are proportional to the square of the magnetic field. Deconvoluting these contributions is further complicated by residue-dependent variations in protein amide (15)N CSA values which have proven difficult to accurately measure. Exploiting recently reported improvements for the implementation of T1 and T1ρ experiments, field strength-dependent studies have been carried out on the B3 domain of protein G (GB3) as well as on the immunophilin FKBP12 and a H87V variant of that protein in which the major conformational exchange linebroadening transition is suppressed...
November 2016: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/27720433/autumnalamide-targeted-proteins-of-the-immunophilin-family
#16
Jon Andoni Sánchez, Amparo Alfonso, Olivier P Thomas, Luís M Botana
Previous works with autumnalamide reported that Store Operated Calcium (SOC) channels were blocked through mitochondrial modulation. In the present paper we studied the effect of autumnalamide on ionomycin Ca(2+) fluxes. Thus, autumnalamide did not modify ionomycin-sensitive intracellular pools while the ionomycin-induced Ca(2+) influx was blocked with similar potency whether the incubation was done before or after ionomycin-sensitive pools depletion. Nevertheless, autumnalamide was not able to inhibit ionomycin-induced Ca(2+) influx once the membrane channels were activated...
February 2017: Immunobiology
https://www.readbyqxmd.com/read/27670942/total-chemical-synthesis-refolding-and-crystallographic-structure-of-fully-active-immunophilin-calstabin-2-fkbp12-6
#17
Marine Bacchi, Magali Jullian, Serena Sirigu, Benjamin Fould, Tiphaine Huet, Lisa Bruyand, Mathias Antoine, Laurent Vuillard, Luisa Ronga, Leonard M G Chavas, Olivier Nosjean, Gilles Ferry, Karine Puget, Jean A Boutin
Synthetic biology (or chemical biology) is a growing field to which the chemical synthesis of proteins, particularly enzymes, makes a fundamental contribution. However, the chemical synthesis of catalytically active proteins (enzymes) remains poorly documented because it is difficult to obtain enough material for biochemical experiments. We chose calstabin, a 107-amino-acid proline isomerase, as a model. We synthesized the enzyme using the native chemical ligation approach and obtained several tens of milligrams...
December 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/27641460/a-%C3%AE-turn-motif-in-the-steroid-hormone-receptor-s-ligand-binding-domains-interacts-with-the-peptidyl-prolyl-isomerase-ppiase-catalytic-site-of-the-immunophilin-fkbp52
#18
Cillian Byrne, Morkos A Henen, Mathilde Belnou, François-Xavier Cantrelle, Amina Kamah, Haoling Qi, Julien Giustiniani, Béatrice Chambraud, Etienne-Emile Baulieu, Guy Lippens, Isabelle Landrieu, Yves Jacquot
The immunophilin FKBP52 interacts with nuclear steroid hormone receptors. Studying the crystal structure of human estrogen receptor α (hERα) and using nuclear magnetic resonance, we show here that the short V(364)PGF(367) sequence, which is located within its ligand-binding domain and adopts a type II β-turn conformation in the protein, binds the peptidyl-prolyl isomerase (PPIase or rotamase) FK1 domain of FKBP52. Interestingly, this turn motif displays strong similarities with the FKBP52 FK1 domain-binding moiety of macrolide immunomodulators such as rapamycin and GPI-1046, an immunophilin ligand with neuroprotective characteristics...
September 27, 2016: Biochemistry
https://www.readbyqxmd.com/read/27503910/hsp90-binding-immunophilin-fkbp52-modulates-telomerase-activity-by-promoting-the-cytoplasmic-retrotransport-of-htert
#19
Yu Young Jeong, Joonyoung Her, Sue-Young Oh, In Kwon Chung
Telomerase is a unique ribonucleoprotein enzyme that is required for continued cell proliferation. To generate catalytically active telomerase, human telomerase reverse transcriptase (hTERT) must translocate to the nucleus and assemble with the RNA component of telomerase. The molecular chaperones heat shock protein 90 (Hsp90) and p23 maintain hTERT in a conformation that enables nuclear translocation. However, the regulatory role of chaperones in nuclear transport of hTERT remains unclear. In this work, we demonstrate that immunophilin FK506-binding protein (FKBP)52 linked the hTERT-Hsp90 complex to the dynein-dynactin motor, thereby promoting the transport of hTERT to the nucleus along microtubules...
October 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27479154/caspase-cleaved-tau-d-421-is-colocalized-with-the-immunophilin-fkbp52-in-the-autophagy-endolysosomal-system-of-alzheimer-s-disease-neurons
#20
Geri Meduri, Kevin Guillemeau, Omar Dounane, Véronique Sazdovitch, Charles Duyckaerts, Béatrice Chambraud, Etienne Emile Baulieu, Julien Giustiniani
Pathologic modifications of the Tau protein leading to neurofibrillary tangle (NFT) formation are a common feature of a wide range of neurodegenerative diseases known as tauopathies, which include Alzheimer's disease (AD). We previously showed that the immunophilin FKBP52 physically and functionally interacts with Tau, and we recently reported that FKBP52 levels are abnormally low in AD patients' brains. To decipher the mechanism of FKBP52 decrease in AD brains, we performed multiple labeling immunohistofluorescence and lysosomal purification using postmortem brain samples of healthy controls (n = 8) and AD (n = 20) patients...
October 2016: Neurobiology of Aging
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