O glcnac in cancer biology book

Chemical biology of glycoproteins by zhongping tan. Nacetylglucosamine oglcnac at serine or threonine residues. Since many of these cancers also had increased ogt rna and protein levels, it is not clear whether elevated oglcnacylation is due to increased. A number of labs have seen similar reduction in tumor cell growth when ogt or oglcnacylation is reduced. Dnacetylglucosamine glcnac sugars to serine or threonine residues of nuclear and cytoplasmic proteins, and it is involved in extensive crosstalk with other posttranslational modifications, such as phosphorylation. The results of recent studies suggest that oglcnacylation, which involves the addition of nacetylglucosamine on the serine or threonine residues of proteins, may play a. O glcnacylation and phosphorylation are two posttranslational modifications that antagonistically regulate protein function.

Mechanistically, reducing oglcnac levels in breast cancer cells led to g1 cell cycle arrest and increased proteasomal degradation of the oncogenic transcription factor foxm1, causing a decrease in multiple foxm1specific targets, including sphase kinaseassociated protein 2, and a concomitant increase in cyclindependent kinase inhibitor p27. Oglcnacylation of proteins for effective use of sugar under stress and deprivation conditions is one of the adaptive responses of the cancerous cells and further research is needed to. This book chapter describes nonradioactive colorimetric assays for glycosyltransferases and sulfotransferases. Jaskiewicz 1,2, crystal hermawan1, stephanie parisi1 and david h.

Nacetylglucosamine oglcnac is a highly dynamic intracellular protein modification responsive to stress, hormones, nutrients, and cell cycle stage. This oglcnacylation is a dynamic posttranslational modification similar to phosphorylation. Nacetylglucosamine oglcnac moiety linked to the serine or threonine residues in proteins. Ogt, oglcnac, sox2, pancreatic cancer, metabolism, selfrenewal. Immunoblotting analysis using the oglcnacspecific antibodies has indicated that glucose deprivation increases protein oglcnacylation in some cancer cells. Townson 1department of molecular cellular and biomedical sciences, university of new hampshire, new hampshire, durham, nh, usa. Reginato1,5 1department of biochemistry and molecular biology, drexel university college of medicine, philadelphia, pa 19102, usa. Increased total oglcnacylation is emerging as a general characteristic of cancer cells, and recent studies suggest that oglcnacylation is a central. Here we investigated the role of o glcnacylation during vernalization, a process whereby prolonged cold exposure promotes. It appears that oglcnac is part of the histone code, regulating gene transcription in an epigenetic manner.

Finally, oglycosylated glycoproteins may be important during reproduction and fertilization. Nacetylglucosamine oglcnac, which was discovered in the early 1980s, is the covalent addition of a glcnac sugar. Oglcnac was termed a nutritional sensor, as global levels of the modification are elevated in response to increased glucose and glutamine flux into the hexosamine biosynthetic pathway. Oglcnac transferase regulates cancer stemlike potential of. Oglcnacylation levels are found elevated in nearly all cancers examined. Functional roles of oglcnac in cell signaling yonsei. Oglcnac was termed a nutritional sensor, as global levels of the. Nactylglucosamine oglcnac is a carbohydrate posttranslational modification on hydroxyl groups of serine andor threonine residues of cytosolic and nuclear proteins. The potential role of oglcnac modification in cancer epigenetics the lectinbinding pattern of nucleolin and its interaction with endogenous galectin3 mir375 induces human decidua basalisderived stromal cells to become insulinproducing cells. O glcnac transferase is a part of a host of biological functions within the human body. Ogt is involved in the resistance of insulin in muscle cells and adipocytes by inhibiting the threonine 308 phosphorylation of akt1, increasing the rate of irs1 phosphorylation at serine 307 and serine 632635, reducing insulin signaling, and.

The potential role of oglcnac modification in cancer. The biology of cancer is a textbook for undergraduate and graduate biology students as well as medical students studying the molecular and cellular bases of cancer. Oglcnac signaling in cancer metabolism and epigenetics. The single mammalian ogt gene is located on the human x chromosome near the xist locus and encodes multiple alternatively spliced isoforms of ogt targeted to these different intracellular. Oglcnacylation regulates breast cancer metastasis via sirt1 modulation of foxm1 pathway christina m.

This novel mechanism where oglcnacylation regulates cancer cell metabolic reprograming via regulation of hif1. Inhibition of oglcnac transferase activity reprograms prostate cancer cell metabolism harri m. Oglcnac in cancer cell biology o glcnacylation is catalysed by a single enzyme, termed o linked n acetylglucosamine transferase ogt, which transfers n acetylglucosamine from uridine diphosphate n acetylglucosamine udpglcnac to protein substrates 7. N2 olinked nacetylglucosamine oglcnac is a dynamic nutrient sensor that regulates nearly all aspects of cellular physiology see oglcnacylation. Inhibition of oglcnac transferase activity reprograms. A conserved splicing silencer dynamically regulates oglcnac transferase intron retention and o. Cancer metabolism and elevated oglcnac in oncogenic signaling. However, the regulation of and the cross talk between these two protein modifications are poorly understood in plants. Department of molecular biology and biochemistry and department of chemistry, simon fraser university, 8888 university dr, burnaby, bc, v5a 1s6, canada. In addition, we identify klf8 as a novel regulator of breast cancer mammosphere formation and a critical target of ogt in regulating cancer. Cessation of chronic ethanol usage can raise the level of sensitivity of the mind to excitotoxic problems. This chapter presents an overview of the function of oglcnac modification in various signaling pathways.

Oglcnac, an essential regulator of numerous cellular pathways. Oglcnac is added by the enzyme ogt to serine and threonine of target proteins in the cytoplasm, nucleus, and mitochondrion 27, 28. This aberrant oglcnacylation correlates with augmented tumor cell proliferation and survival, increased tumor formation, invasion, metastasis, and resistance to therapy. Mechanistic insights of oglcnacylation that promote progression of cholangiocarcinoma cells via nuclear translocation of nf.

Oglcnacylation enhances the tumorigenic properties of cervical cancer cells in vitro nicole m. Aglycosylation is a feature of engineered antibodies to bypass glycosylation. Nacetylglucosamine oglcnac is an intracellular carbohydrate that dynamically modifies the amino acids serine and threonine through their hydroxyl moieties on nuclear and cytoplasmic proteins. Numerous studies indicate that oglcnac promotes cancer cell invasiveness and metastasis. Understanding how this altered metabolism is regulated has recently emerged as an intense research focus in cancer biology. Analogous to phosphorylation, oglcnacylation plays crucial regulatory roles in a variety of cellular processes.

This neuroprotection could possibly be explained with a reduction in nmdastimulated calcium mineral influx following the administration of hu210, discovered specifically in ethanolwithdrawn neurons. Thus, manipulation of oglcnac levels using chemical or shrnamediated inhibition of oga or ogt affects in vitro and in vivo migrationinvasion of breast 31, 112, 121, lung 31, 33, liver, prostate, and colon cancer cells. Advances in functional genetic screens with transposons and crisprcas9 to illuminate cancer biology. Identification of novel proteins differentially expressed in pluripotent. Oglcnacylation is a dynamic posttranslational modification involved in a wide range of biological processes and diseases such as cancer. Ab many nuclear and cytosolic proteins are modified with olinked. Both h2b ser36 and h4 ser47 are found on the lateral surface of the nucleosome and contact the dna either directly in the case of h2b ser36 or indirectly in the case of h4 ser47 46. Taken together, oglcnac appears to be important in tumor biology, and altered oglcnacylation is an event found in many types of cancer. Oglcnac is essential for cell survival and plays important role in many biological processes e. Natasha zachara on oglcnac, an essential regulator of numerous cellular pathways, part of a collection of online lectures.

Cervical cancer is the leading cause of cancerrelated death in women worldwide. Oglcnacylation regulates breast cancer metastasis via. The encyclopedia of cell biology offers a broad overview of cell biology, offering reputable, foundational content for researchers and students across the biological and medical sciences. As a form of protein glycosylation, it differs from most other forms in three aspects. Similar to phosphorylation, olinked nacetylglucosamine oglcnac modification of nuclear and cytosolic proteins is an abundant, dynamic, and. Thus, understanding the regulation of oglcnacylation in tumor cells and their. In this report we present experimental evidence suggesting that the epidermal growth factor receptor egfr is.

Oglcnac and the epigenetic regulation of gene expression. Circulating exosomes for early diagnosis of pancreatic cancer. A better understanding of oglcnac signaling in cancer initiation, progression and metastasis would help to identify new targets that can be used for diagnosis, prevention, and treatment of human cancer. We also discuss inhibition of hyperoglcnacylation as a potential novel. The tmas were quantitated independently and blindly by 3 research. This important work includes 285 articles from domain experts covering every aspect of cell biology, with fully annotated figures, abundant illustrations. Diet and environmental factors can alter the scope of epigenetic regulation. Circulating exosomes for early diagnosis of pancreatic cancer 1 reply the best way to cure cancer is to catch it early when surgical removal of a localized mass can successfully rid the patient of all cancer cells and cancer stem cells. Cancer metabolism and elevated o glcnac in oncogenic. O glcnac is found on each of the core histones with sites mapped to h2a thr101, h2b ser36 and h4 ser47 ref. Oglcnac, glucose deprivation and cancer antibody news. Cancer cells exhibit increased uptake of glucose and glutamine, and rewire the metabolic flux toward anabolic pathways important for cell growth and proliferation.

This book aims to promote more research for improved understanding of protein glycosylation and its application to commercial products. A single pair of enzymes o glcnac transferase ogt and o glcnacase. In cancer, it was observed that the biosynthesis of ogalnac glycans is often abnormal, which may affect the biology and survival of the cancer cell. O glcnacylation is a nutrient and stressresponsive posttranslational modification ptm that involves the attachment of o linked n acetylglucosamine moieties to ser and thr residues of cytoplasmic, nuclear and mitochondrial proteins. The enzymes that catalyze the addition and removal of oglcnac have been cloned and characterized. Park sk, zhou x, pendleton k, hunter ov, kohler jj, odonnell ka, conrad nk 2017. Distinguished research professor of biochemistry and molecular biology. A unique feature of cancer cell energy metabolism is a shift from oxidative phosphorylation to the less efficient glycolytic pathway warburg effect, necessitating greatly increased glucose uptake. Oglcnacylation of the human epidermal growth factor. Book chapters are listed at the bottom of this page. The clarity of writing and the lucid fullcolor art program make the book accessible and engaging. Knockdown of ogt reduces cancer cell hyperoglcnacylation and inhibits. Novel cytoplasmic glycosylation of proteins in signal transduction. One of the remarkable features of cancer cells is aerobic glycolysis, a phenomenon also known as the warburg effect 18 20, in which cancer cells rely preferentially on glycolysis instead of oxidative phosphorylation as the main energy source even in the presence of high oxygen tension.

A mitotic glcnacylationphosphorylation signaling complex. Dnacetylglucosamine glcnac moieties to serinethreonine residues in target proteins is a frequently occurring posttranslational modification affecting the functionality of many cellular systems. Oglcnacylation is becoming increasing realized as having important roles in cancerrelevant processes, such as. Regulation of jakstat signalling in the immune system. Oglcnac modification of sox2 regulates selfrenewal in pancreatic. Oglcnacylation enhances the tumorigenic properties of. Oglcnac modification of histone h2b facilitates its monoubiquitination, associated with active gene transcription. Purchase glycosylation and cancer, volume 126 1st edition. Oglcnac expression levels epigenetically regulate colon cancer tumorigenesis by affecting the cancer stem cell compartment via modulating expression of. Roles of regulatory posttranslational modifications, in particular oglycosylation, in increasing functional diversity of proteins. Therefore, oglcnac signaling may play a central role in integrating metabolic and epigenetic reprogramming in cancer. The book presents the principles of cancer biology in an organized, cogent, and indepth manner. Detecting oglcnac using in vitro sulfation glycobiology. Nacetylglucosaminylation oglcnacylation, has been discovered in many types of epithelial cancers, including those of the female reproductive tract, but the role it potentially plays in cellular growth and metastasis is unclear.