Editorial Cite This: Chem. Rev. 2018, 118, 887−888
pubs.acs.org/CR
Introduction: Posttranslational Protein Modification
O
The investigation of PTMs has been greatly facilitated by new technologies. The advances in mass spectrometry have allowed proteome-wide identifications of PTMs under various genetic or environmental manipulations. Various PTM-specific antibodies and chemical probes have been developed that enable the detection and investigation of PTMs. Furthermore, small molecule inhibitors of writers, readers, and erasers allow facile pharmacological control of PTMs, which facilitates the investigation of their biological functions. Given that PTMs are involved in essentially all life processes and integrate various disciplines (chemistry, biochemistry, molecular and cell biology, structural biology, proteomics, metabolomics, and genetics), they are also indispensable as a biomedical research area. PTMs hold tremendous potential for biology and medicine and, thus, require continuous research attention. This thematic issue of Chemical Reviews is dedicated to various PTMs, including acetylation, lipidation, proteolysis, ADP-ribosylation, persulfidation, AMPylation, disulfide formation, phosphorylation, methylation, nitration, and ubiquitinlike modifications. The authors of these articles provide comprehensive reviews on these PTMs, including fundamental mechanisms, key challenges in the field, and opportunities for therapeutics development. It is our hope that these articles will not only provide excellent teaching materials for anyone interested in learning these topics but also capture the frontiers of the topics and stimulate new research interest. Enjoy reading!
ur genome encodes about 20,000 genes, which are transcribed into mRNA and then translated into proteins. Proteins perform numerous biochemical functions and are central for all life processes, including metabolism, signal transduction, transcription, translation, cellular structural integrity, and cell movement. A common feature of all living organisms is the ability to adapt to and survive the changing environment. In order to respond to environmental changes, the proteins of a living organism, or the proteome, must change. New proteins may need to be synthesized to deal with an environmental stress. At the same time, existing proteins can undergo certain chemical modifications, commonly referred to as protein post-translational modifications (PTMs), which introduce structural changes in proteins and thus produce signal responses. Dynamic changes in PTMs can occur much faster than the synthesis of new proteins, which allows rapid responses to environmental challenges. In fact, PTM changes often precede and are required for new protein syntheses. For example, histone lysine acetylation and methylation are important for transcription and thus new protein synthesis. Furthermore, compared to the limited proteinogenic amino acids, the number of potential PTMs are much larger, which enable the combinatorial use of different PTMs for dealing with various environmental cues. These features make PTMs particularly important for numerous cell signaling pathways, a point that is increasingly recognized as we understand more about PTMs. Thus, PTMs are essential for various biological processes and are indispensable for life. To make sure that the signaling process is accurate, PTMs have to be carefully controlled. In most cases, specific enzymes are required to add or remove PTMs to defined proteins at specific sites. These enzymes are increasingly called “writers” and “erasers” of PTMs. In many cases, PTMs can be recognized by other protein partners (“readers”), thus enabling protein− protein interactions that are important for the signal transduction. Perturbing PTMs by disrupting (genetically or pharmacologically) the writers, readers, and erasers can change the biological pathways involved and have important therapeutic significance. Many environmental cues are of chemical nature or can lead to changes in cellular small molecules (metabolites). Not surprisingly, many PTMs are closely connected to metabolites. For example, phosphorylation and AMPylation uses adenosine triphosphate (ATP), methylation uses S-adenosyl methione (SAM), lipidation uses acyl-coenzyme A or polyisoprenyl pyrophosphate, and ADP-ribosylation uses nicotinamide adenine dinucleotide (NAD+). Certain reactive small molecules, such as peroxynitrite and hydrogen sulfide, can react with protein side chains, leading to protein nitration and persulfidation, respectively. The intimate connection between PTMs and metabolites allows PTMs to integrate different signals, including the integration of extracellular signal and cellular metabolic state. © 2018 American Chemical Society
Hening Lin*
Howard Hughes Medical Institute and Cornell University
Kate S. Caroll
The Scripps Research Institute
AUTHOR INFORMATION Corresponding Author
*E-mail:
[email protected]. ORCID
Hening Lin: 0000-0002-0255-2701 Notes
Views expressed in this editorial are those of the authors and not necessarily the views of the ACS. Special Issue: Posttranslational Protein Modifications Published: February 14, 2018 887
DOI: 10.1021/acs.chemrev.7b00756 Chem. Rev. 2018, 118, 887−888
Chemical Reviews
Editorial
Biographies
therapeutic approaches. In addition, her group investigates sulfur pathways that are essential for infection and long-term survival of human pathogens such as Mycobacterium tuberculosis. Dr. Carroll currently serves on the editorial board of Cell Chemistry Biology, Molecular Biosystems, and The Journal of Biology Chemistry, and she is a contributing member of “Faculty of 1000”. She is also the recipient of the ACS Pf izer Award in Enzyme Chemistry (2013), Camille Dreyf us Teacher−Scholar Award (2010), Scientist Development Award from American Heart Association (2008), and Special Fellow Award from the Leukemia and Lymphoma Society (2006).
Hening Lin was born in China and obtained his B.S. degree in Chemistry in 1998 from Tsinghua University, Beijing, China. He obtained his Ph.D. degree in 2003 from Columbia University under the guidance of Dr. Virginia Cornish. From 2003 to 2006, he was a Jane Coffin Childs postdoctoral fellow in Dr. Christopher Walsh’s lab at Harvard Medical School. He joined the faculty of Department of Chemistry and Chemical Biology at Cornell University as an Assistant Professor in 2006. He was promoted to associate professor in 2012 and professor in 2013. His lab works at the interface of chemistry, biology, and medicine. The research in his group focuses on NAD+consuming enzymes that have important biological functions and human disease relevance, including poly(ADP-ribose) polymerases and sirtuins. His lab also works on the biosynthesis of diphthamide, the target of diphtheria toxin. His work was recognized by a Dreyfus New Faculty Award in 2006, the CAPA Distinguished Junior Faculty Award in 2011, the 2014 ACS Pfizer Award in Enzyme Chemistry, and the 2016 OKeanos-CAPA Senior Investigator Award. He has been a Howard Hughes Medical Institute investigator since 2015.
Kate S. Carroll is an Associate Professor in the Department of Chemistry at The Scripps Research Institute in Jupiter, Florida. She received her B.A. degree in Biochemistry from Mills College in 1996 and her Ph.D. in Biochemistry from Stanford University in 2003. Her postdoctoral work was completed at the University of California, Berkeley, where she was a Damon Runyon−Walter Winchell Chancer Fund Fellow with Prof. Carolyn Bertozzi. She was an Assistant Professor at the University of Michigan until 2010, when she joined the Chemistry faculty at Scripps. Her research interests span the disciplines of chemistry and biology with an emphasis on studies of sulfur biochemistry pertinent to disease states. Her lab focuses on the development of novel tools to study redox modifications of cysteine thiols, profiling changes in protein oxidation associated with disease and exploiting this information for development of diagnostic and 888
DOI: 10.1021/acs.chemrev.7b00756 Chem. Rev. 2018, 118, 887−888
