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post translation modification

Nathalie Ly, Nadia Elkhatib, Enzo Bresteau, Olivier Piétrement, Mehdi Khaled, Maria M Magiera, Carsten Janke, Eric Le Cam, Andrew D Rutenberg, Guillaume Montagnac
Acetylation of the lysine 40 of α-tubulin (K40) is a post-translational modification occurring in the lumen of microtubules (MTs) and is controlled by the α-tubulin acetyl-transferase αTAT1. How αTAT1 accesses the lumen and acetylates α-tubulin there has been an open question. Here, we report that acetylation starts at open ends of MTs and progressively spreads longitudinally from there. We observed acetylation marks at the open ends of in vivo MTs re-growing after a Nocodazole block, and acetylated segments growing in length with time...
October 18, 2016: Scientific Reports
Qingqing Liu, Tao Tao, Fang Liu, Runzhou Ni, Cuihua Lu, Aiguo Shen
As an essential post-translational modification, O-GlcNAcylation has been thought to be able to modulate various nuclear and cytoplasmic proteins and is emerging as a key regulator of multiple biological processes, such as transcription, cell growth, signal transduction, and cell motility. Recently, authoritative glycomics analyses have reported extensive crosstalk between O-GlcNAcylation and phosphorylation, which always dynamically interplay with each other and regulate signaling, transcription, and other cellular processes...
October 14, 2016: Experimental Cell Research
Fengchao Yu, Ning Li, Weichuan Yu
In computational proteomics, identification of peptides with an unlimited number of post-translational modification (PTM) types is a challenging task. The computational cost associated with database search increases exponentially with respect to the number of modified amino acids and linearly with respect to the number of potential PTM types at each amino acid. The problem becomes intractable very quickly if we want to enumerate all possible PTM patterns. To address this issue, one group of methods named restricted tools (including Mascot, Comet, and MS-GF+) only allow a small number of PTM types in database search process...
October 17, 2016: Journal of Proteome Research
Manabu Koike, Yasutomo Yutoku, Aki Koike
Understanding the molecular mechanisms of DNA double-strand break (DSB) repair processes, especially nonhomologous DNA-end joining (NHEJ), is critical for developing next-generation radiotherapies and chemotherapeutics for human and animal cancers. The localization, protein-protein interactions and post-translational modifications of core NHEJ factors, such as human Ku70 and Ku80, might play critical roles in controlling NHEJ activity. XRCC4-like factor (XLF) is a core NHEJ factor and plays a key role in the Ku-dependent NHEJ repair process in human cells...
October 14, 2016: Journal of Veterinary Medical Science
Evgenia Karousou, Suniti Misra, Shibnath Ghatak, Katalin Dobra, Martin Götte, Davide Vigetti, Alberto Passi, Nikos K Karamanos, Spyros S Skandalis
Synthesis, deposition, and interactions of hyaluronan (HA) with its cellular receptor CD44 are crucial events that regulate the onset and progression of tumors. The intracellular signaling pathways initiated by HA interactions with CD44 leading to tumorigenic responses are complex. Moreover, HA molecules may perform dual functions depending on their concentration and size. Overexpression of variant isoforms of CD44 (CD44v) is most commonly linked to cancer progression, whereas their loss is associated with inhibition of tumor growth...
October 13, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Zhigang Li, Baoyi Liu, Benjie Wang, Yupeng Liu, Yao Zhang, Fengde Tian, Borui Li, Dewei Zhao
Collagen type Ⅱ (col Ⅱ) and aggrecan, the main components of the extracellular matrix (ECM) in human joint cartilage, have been reported to be reduced by chronic production of inflammatory cytokine interleukin (IL)-1β in arthritic joints. Carvedilol, a licensed medicine, has been used for treatment of hypertension, congestive heart failure and coronary disease in clinics. In this study, we investigated the effects of Carvedilol on the expression of col Ⅱ and aggrecan. Our results demonstrate that treatment with Carvedilol didn't change the expression of aggrecan or col Ⅱ at mRNA levels in SW1353 chondrocytes...
October 13, 2016: Biochemical and Biophysical Research Communications
Guoqiang Ma, Shuang Li, Yuhong Han, Shuangxi Li, Tao Yue, Bing Wang, Jin Jiang
Hedgehog (Hh) signaling plays a central role in development and diseases. Hh activates its signal transducer and GPCR-family protein Smoothened (Smo) by inducing Smo phosphorylation, but whether Smo is activated through other post-translational modifications remains unexplored. Here we show that sumoylation acts in parallel with phosphorylation to promote Smo cell-surface expression and Hh signaling. We find that Hh stimulates Smo sumoylation by dissociating it from a desumoylation enzyme Ulp1. Sumoylation of Smo in turn recruits a deubiquitinase UBPY/USP8 to antagonize Smo ubiquitination and degradation, leading to its cell-surface accumulation and elevated Hh pathway activity...
October 7, 2016: Developmental Cell
Ximena Zottig, Mathieu Laporte Wolwertz, Makan Golizeh, Leanne Ohlund, Lekha Sleno, Steve Bourgault
Light chain amyloidosis (AL) originates from the deposition of immunoglobulin light chains (LCs) as amyloid fibrils in the extracellular space of vital organs. Although non-enzymatic post-translational modifications (PTMs) have been shown to contribute to protein misfolding diseases, little is known about their contributions to LC amyloidogenicity. In this study, we investigated the effects of three oxidative PTMs, carbonylation by hydroxynonenal (HNE), oxidation and nitration, on the structure, thermodynamic stability and self-assembly propensity of a LC variable domain from the λ6 germline, Wil...
October 11, 2016: Biophysical Chemistry
Sriram Neelamegham, Lara K Mahal
Glycosylation is a ubiquitous mammalian post-translational modification that both decorates a majority of expressed proteins and regulates their function. Cellular glycan biosynthesis is facilitated by a few hundred enzymes that are collectively termed 'glycoenzymes'. The expression and activity of these enzymes is controlled at the transcription, translation and post-translation levels. New wet-lab advances are providing analytical methods to collect large-scale data at these multiple levels, relational databases are starting to collate these results, and computer models are beginning to integrate this information across scales in order to gain new knowledge...
October 13, 2016: Current Opinion in Structural Biology
Julie A Poposki, Aiko I Klingler, Whitney W Stevens, Anju T Peters, Kathryn E Hulse, Leslie C Grammer, Robert P Schleimer, Kevin C Welch, Stephanie S Smith, Douglas M Sidle, David B Conley, Bruce K Tan, Robert C Kern, Atsushi Kato
RATIONALE: Thymic stromal lymphopoietin (TSLP) is known to be elevated and truncated in nasal polyps (NPs) of chronic rhinosinusitis and might play a significant role in type 2 inflammation in this disease. However, neither the structure nor the role of the truncated products of TSLP has been studied. OBJECTIVE: To investigate the mechanisms of truncation of TSLP in NPs and the function of the truncated products. METHODS: We incubated recombinant human TSLP with NP extracts, and determined the protein sequence of the truncated forms of TSLP using Edman protein sequencing and MALDI-TOF mass spectrometry (MS)...
October 12, 2016: Journal of Allergy and Clinical Immunology
Shengyuan Zeng, Yangyang Wang, Ting Zhang, Lu Bai, Yalan Wang, Changzhu Duan
UHRF2 is a ubiquitin-protein ligase E3 that regulates cell cycle, genomic stability and epigenetics. We conducted a co-immunoprecipitation assay and found that TIP60 and HDAC1 interact with UHRF2. We previously demonstrated that UHRF2 regulated H3K9ac and H3K14ac differentially in normal and cancer cells. However, the accurate signal transduction mechanisms were not clear. In this study, we found that TIP60 acted downstream of UHRF2 to regulate H3K9ac and H3K14ac expression. TIP60 is stabilized in normal cells by UHRF2 ubiquitination...
October 14, 2016: Protein & Cell
Serena Marcelli, Elena Ficulle, Filomena Iannuzzi, Enikö Kövari, Robert Nisticò, Marco Feligioni
Synaptic dysfunction has been recognized as an early feature occurring at the onset of Alzheimer's disease (AD). Compromised neurotransmission leads over time to synaptic loss and these events correlate with the cognitive decline that progressively affects AD patients.Protein SUMOylation (Small Ubiquitin-like MOdifier) is a post-translational modification (PTM) involved in several cellular processes including synaptic transmission.We here demonstrate that cortical synaptosomes prepared from Tg2576 mice of 6 months of age show an increased SUMO-1ylation, which returns back to normal levels at 20 months although synaptic SUMOylation, at this age, resulted more sensible to KCl stimulus...
October 13, 2016: Molecular Neurobiology
Aneeqa Noor, Saadia Zahid
Synaptosomal-associated protein 25 kDa (SNAP-25) is one of the key proteins involved in formation of neural soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, which are responsible for the calcium-dependent exocytosis of neurotransmitters - a major step in neurotransmission and the key to normal functioning of brain. Several studies have reported abnormalities in its expression and structure and highlighted it as an important player in pathology of various neurological disorders like Alzheimer's disease, schizophrenia, attention deficient hyperactivity disorder, epilepsy and few others...
October 13, 2016: International Journal of Neuroscience
Mi Suk Lee, Hyo-Jung Choi, Eui-Jung Park, Hye-Jeong Park, Tae-Hwan Kwon
Carboxyl-terminus of AQP2 (AQP2c) undergoes post-translational modifications, including phosphorylation and ubiquitination, for the regulation of aquaporin-2 (AQP2) translocation and protein abundance. We aimed to identify novel proteins interacting with AQP2c. Recombinant AQP2c protein was made in E. coli BL21 (DE3) by exploiting the pET32 TrxA fusion system. Lysates of rat kidney inner medullary collecting duct (IMCD) tubule suspensions interacted with rat AQP2c bound to Ni(2+)-resin were subjected to LC-MS/MS proteomic analysis...
October 12, 2016: American Journal of Physiology. Renal Physiology
Tycho E T Mevissen, Yogesh Kulathu, Monique P C Mulder, Paul P Geurink, Sarah L Maslen, Malte Gersch, Paul R Elliott, John E Burke, Bianca D M van Tol, Masato Akutsu, Farid El Oualid, Masato Kawasaki, Stefan M V Freund, Huib Ovaa, David Komander
The post-translational modification of proteins with polyubiquitin regulates virtually all aspects of cell biology. Eight distinct chain linkage types co-exist in polyubiquitin and are independently regulated in cells. This 'ubiquitin code' determines the fate of the modified protein. Deubiquitinating enzymes of the ovarian tumour (OTU) family regulate cellular signalling by targeting distinct linkage types within polyubiquitin, and understanding their mechanisms of linkage specificity gives fundamental insights into the ubiquitin system...
October 12, 2016: Nature
Daniel Ian McSkimming, Shima Dastgheib, Timothy R Baffi, Dominic P Byrne, Samantha Ferries, Steven Thomas Scott, Alexandra C Newton, Claire E Eyers, Krzysztof J Kochut, Patrick A Eyers, Natarajan Kannan
Multiple sequence alignments (MSAs) are a fundamental analysis tool used throughout biology to investigate relationships between protein sequence, structure, function, evolutionary history, and patterns of disease-associated variants. However, their widespread application in systems biology research is currently hindered by the lack of user-friendly tools to simultaneously visualize, manipulate and query the information conceptualized in large sequence alignments, and the challenges in integrating MSAs with multiple orthogonal data such as cancer variants and post-translational modifications, which are often stored in heterogeneous data sources and formats...
October 12, 2016: Molecular BioSystems
Tatiana Traboulsi, Mohamed El Ezzy, James Gleason, Sylvie Mader
About 70% of breast tumors express estrogen receptor alpha (ERα), which mediates the proliferative effects of estrogens on breast epithelial cells, and are candidates for treatment with antiestrogens, steroidal or non-steroidal molecules designed to compete with estrogens and antagonize ERs. The variable patterns of activity of antiestrogens (AEs) in estrogen target tissues and the lack of systematic cross-resistance between different types of molecules have provided evidence for different mechanisms of action...
October 11, 2016: Journal of Molecular Endocrinology
Abul Arif, Jie Jia, Dalia Halawani, Paul L Fox
Phosphorylation of many aminoacyl tRNA synthetases (AARSs) has been recognized for decades, but the contribution of post-translational modification to their primary role in tRNA charging and decryption of genetic code remains unclear. In contrast, phosphorylation is essential for performance of diverse noncanonical functions of AARSs unrelated to protein synthesis. Phosphorylation of glutamyl-prolyl tRNA synthetase (EPRS) has been investigated extensively in our laboratory for more than a decade, and has served as an archetype for studies of other AARSs...
October 8, 2016: Methods: a Companion to Methods in Enzymology
Inês M Luís, Bruno M Alexandre, M Margarida Oliveira, Isabel A Abreu
Often plant tissues are recalcitrant and, due to that, methods relying on protein precipitation, such as TCA/acetone precipitation and phenol extraction, are usually the methods of choice for protein extraction in plant proteomic studies. However, the addition of precipitation steps to protein extraction methods may negatively impact protein recovery, due to problems associated with protein re-solubilization. Moreover, we show that when working with non-recalcitrant plant tissues, such as young maize leaves, protein extraction methods with precipitation steps compromise the maintenance of some labile post-translational modifications (PTMs), such as phosphorylation...
2016: PloS One
Li Hui Wu, Xiao Ting Shao, Jun Xia Guo, Hui Sun, Qi Chen, Jing Pan, Qian Qian Cai, Yi Wei Dong, Zhong Yi Chen, Xiao Mei Yan, Min Peng, Nanbert Zhong, Xing Zhong Wu
Sialic acid modification is a kind of post-translational modification. To investigate the regulation effect of sialic acid on neural differentiation, we used CycloManN propanyl perac (CycloManN pro), a metabolic precursor of sialic acid, to treat PC12 cells. We noted that CycloManN pro indeed robustly promoted global sialylation detected by MAL II lectin blot in PC12 cells. Simultaneously, we interestingly found that the neurite outgrowth of PC12 cells was significantly promoted by the CycloManN pro treatment...
October 10, 2016: Glycoconjugate Journal
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