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Tony Y Hu, Fuyuhiko Tamanoi
No abstract text is available yet for this article.
2017: Enzymes
Douglas F Lake
The intracellular compartments for proteolytic antigen processing in tumor cells produce peptides that are presented by MHC molecules to T cells. But first, the ubiquitin ligase system tags defective, misfolded, aged, and unstable proteins for degradation through the proteasome. Ubiqitinated proteins are unfolded and fed into the barrel-shaped core of the proteasome where a collection of multiple different proteases cleave proteins into oligopeptides. After exiting the proteasome, these oligopeptides are either completely degraded into amino acids or trimmed at the N- and C-termini so that they bind to transporter associated with antigen processing (TAP)...
2017: Enzymes
Qian Sun, Zhen Zhao
Peptide hormones represent a major class of hormones that are made from amino acids by specialized endocrine glands. The maturation of bioactive hormones take place in the rough endoplasmic reticulum and Golgi apparatus, where preprohormones are proteolytically cleaved into prohormones, and subsequently into mature peptide hormones. Once the bioactive hormones are released into the circulation, they interact with receptors located on the plasma membrane of target cells, and initiate intracellular signaling pathways to regulate physiological processes including energy metabolism, growth, stress, and reproduction...
2017: Enzymes
David W Greening, Eugene A Kapp, Richard J Simpson
Peptides play a seminal role in most physiological processes acting as neurotransmitters, hormones, antibiotics, and immune regulation. In the context of tumor biology, it is hypothesized that endogenous peptides, hormones, cytokines, growth factors, and aberrant degradation of select protein networks (e.g., enzymatic activities, protein shedding, and extracellular matrix remodeling) are fundamental in mediating cancer progression. Analysis of peptides in biological fluids by mass spectrometry holds promise of providing sensitive and specific diagnostic and prognostic information for cancer and other diseases...
2017: Enzymes
Joel Y Hayashi, Fuyuhiko Tamanoi
Alterations of enzyme activity or enzyme levels in cancer tissue have been documented over the years. Taking advantage of these observations, various strategies for drug activation and drug delivery have been developed. One example is a mechanism called "prodrugs" that generates active drugs by enzyme cleavage. Another example is enzyme-induced anticancer drug release mechanisms. This system is constructed by incorporating enzyme-sensitive linkages to materials such as hydrogels and nanodelivery vehicles, including liposomes, polymer micelles, and mesoporous silica nanoparticles...
2017: Enzymes
Taichiro Nonaka, David T W Wong
Exosomes are small membrane vesicles of endocytic origin that are secreted by most cells and detected in saliva. Pathophysiological roles for salivary exosomes are beginning to be recognized in diseases including cancer, highlighting potential biomarkers and biological functions. Since early detection of cancer is vital for successful treatment, salivary exosomes would be advantageous in achieving a better survival rate due to their ready availability and noninvasiveness. The use of salivary exosomes may therefore be promising in the accurate detection of premalignant lesions and early-stage cancers, also for better our understanding of the molecular basis of tumorigenesis...
2017: Enzymes
Tanxi Cai, Fuquan Yang
Low-molecular-weight region (LMW, MW≤30kDa) of human serum/plasma proteins, including small intact proteins, truncated fragments of larger proteins, along with some other small components, has been associated with the ongoing physiological and pathological events, and thereby represent a treasure trove of diagnostic molecules. Great progress in the mining of novel biomarkers from this diagnostic treasure trove for disease diagnosis and health monitoring has been achieved based on serum samples from healthy individuals and patients and powerful new approaches in biochemistry and systems biology...
2017: Enzymes
Jia Fan, Bo Ning, Christopher J Lyon, Tony Y Hu
Mammalian proteases segregate into several distinct protein families that employ different functional domains to hydrolyze peptides bonds with different specificities and affinities. These enzymes play central roles in critical cellular and systemic processes, including regulation of cell growth, differentiation, homeostasis, and apoptosis; and cancer initiation, progression, and metastasis. Human proteases segregate into five distinct catalytic classes; the metalloprotease, serine protease, and cysteine protease families have the most members, while the aspartic and threonine peptidase families have relatively few examples...
2017: Enzymes
Guillaume F Chanfreau
No abstract text is available yet for this article.
2017: Enzymes
Ya-Ming Hou, Ryuma Matsubara, Ryuichi Takase, Isao Masuda, Joanna I Sulkowska
TrmD is an S-adenosyl methionine (AdoMet)-dependent methyl transferase that synthesizes the methylated m1 G37 in tRNA. TrmD is specific to and essential for bacterial growth, and it is fundamentally distinct from its eukaryotic and archaeal counterpart Trm5. TrmD is unusual by using a topological protein knot to bind AdoMet. Despite its restricted mobility, the TrmD knot has complex dynamics necessary to transmit the signal of AdoMet binding to promote tRNA binding and methyl transfer. Mutations in the TrmD knot block this intramolecular signaling and decrease the synthesis of m1 G37-tRNA, prompting ribosomes to +1-frameshifts and premature termination of protein synthesis...
2017: Enzymes
Katherine M McKenney, Mary Anne T Rubio, Juan D Alfonzo
All types of nucleic acids in cells undergo naturally occurring chemical modifications, including DNA, rRNA, mRNA, snRNA, and most prominently tRNA. Over 100 different modifications have been described and every position in the purine and pyrimidine bases can be modified; often the sugar is also modified [1]. In tRNA, the function of modifications varies; some modulate global and/or local RNA structure, and others directly impact decoding and may be essential for viability. Whichever the case, the overall importance of modifications is highlighted by both their evolutionary conservation and the fact that organisms use a substantial portion of their genomes to encode modification enzymes, far exceeding what is needed for the de novo synthesis of the canonical nucleotides themselves [2]...
2017: Enzymes
Guillaume F Chanfreau
Constitutive and regulated turnover of RNAs is necessary to eliminate aberrant RNA molecules and control the level of specific mRNAs to maintain homeostasis or to respond to signals in living cells. Modifications of nucleosides in specific RNAs are important in modulating the functions of these transcripts, but they can also dramatically impact their fate and turnover. This chapter will review how RNA modifications impact the activities of ribonucleases that target these RNAs for degradation or cleavage, focusing more particularly on tRNAs and mRNAs in eukaryotic cells...
2017: Enzymes
Lee E Vandivier, Brian D Gregory
Ribonucleotides can be covalently modified with over 100 known chemical moieties, greatly expanding the potential coding and regulatory repertoire of RNA. Recent advances in applying high-throughput sequencing to the study of RNA modifications have generated transcriptome-wide modification maps and demonstrated that modifications are abundant features of multiple classes of RNAs, including messenger RNAs. In turn, new regulatory functions for RNA modifications have been elucidated. Here, we review both targeted and global methods for surveying RNA modification, with a focus on how transcriptome-wide methods have helped expand the understanding of modification-mediated regulation of the transcriptome...
2017: Enzymes
Yuru Wang, Yuxuan Zheng, Peter A Beal
Inosine is one of the most common modifications found in human RNAs and the Adenosine Deaminases that act on RNA (ADARs) are the main enzymes responsible for its production. ADARs were first discovered in the 1980s and since then our understanding of ADARs has advanced tremendously. For instance, it is now known that defective ADAR function can cause human diseases. Furthermore, recently solved crystal structures of the human ADAR2 deaminase bound to RNA have provided insights regarding the catalytic and substrate recognition mechanisms...
2017: Enzymes
Anthony K Henras, Célia Plisson-Chastang, Odile Humbert, Yves Romeo, Yves Henry
Ribosomal RNAs contain numerous 2'-O-methylated nucleosides and pseudouridines. Methylation of the 2' oxygen of ribose moieties and isomerization of uridines into pseudouridines are catalyzed by C/D and H/ACA small nucleolar ribonucleoprotein particles, respectively. We review the composition, structure, and mode of action of archaeal and eukaryotic C/D and H/ACA particles. Most rRNA modifications cluster in functionally crucial regions of the rRNAs, suggesting they play important roles in translation. Some of these modifications promote global translation efficiency or modulate translation fidelity...
2017: Enzymes
Meemanage D De Zoysa, Yi-Tao Yu
Pseudouridine (Ψ) is the most abundant posttranscriptional modification in noncoding RNAs. Pseudouridines are often clustered in important regions of rRNAs (ribosomal RNAs), snRNAs (small nuclear RNAs), and tRNAs (transfer RNAs), contributing to RNA function. Pseudouridylation is governed by two independent mechanisms. The first involves single protein enzymes called pseudouridine synthases (PUSs) that alone recognize the substrate and catalyze the isomerization of uridine to pseudouridine (RNA-independent pseudouridylation)...
2017: Enzymes
Olga Kolaj-Robin, Bertrand Séraphin
Elongator is a highly conserved eukaryotic protein complex consisting of two sets of six Elp proteins, while homologues of its catalytic subunit Elp3 are found in all the kingdoms of life. Although it was originally described as a transcription elongation factor, cumulating evidence suggests that its primary function is catalyzing tRNA modifications. In humans, defects in Elongator subunits are associated with neurological disorders and cancer. Although further studies are still required, a clearer picture of the molecular mechanism of action of Elongator and its cofactors has started to emerge within recent years that have witnessed significant development in the field...
2017: Enzymes
Paul F Agris, Amithi Narendran, Kathryn Sarachan, Ville Y P Väre, Emily Eruysal
The posttranscriptional modifications of tRNA's anticodon stem and loop (ASL) domain represent a third level, a third code, to the accuracy and efficiency of translating mRNA codons into the correct amino acid sequence of proteins. Modifications of tRNA's ASL domain are enzymatically synthesized and site specifically located at the anticodon wobble position-34 and 3'-adjacent to the anticodon at position-37. Degeneracy of the 64 Universal Genetic Codes and the limitation in the number of tRNA species require some tRNAs to decode more than one codon...
2017: Enzymes
Chentao Lin, Sheng Luan, Fuyuhiko Tamanoi
No abstract text is available yet for this article.
2016: Enzymes
D Chandran, M C Wildermuth
Recent studies have revealed that several mutualistic and parasitic biotrophic microbes induce a cell cycle variant termed the endocycle in host cells to support their growth and reproduction. Endoreduplication is a process in which cells successively replicate their genomes without mitosis resulting in an increase in nuclear DNA ploidy. Depending on the interaction, endoreduplication can support biotroph colonization and feeding structure initiation/development, and/or serve as a mechanism to support enhanced metabolic demands of the microbe...
2016: Enzymes
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