Signal Seeker PTM Tools
Although there are over 200 types of PTMs described in the literature, there are only a handful that have been studied in great detail, of these serine/threonine phosphorylation, tyrosine phosphorylation (pY), acetylation (Ac), ubiquitination (Ub) and SUMOylation (SUMO) have been shown to be key regulators in almost all cellular processes, including signal transduction, epigenetics, gene and protein expression, protein stability and localization, and cellular immunity. Learn more about these key regulatory protein modifications and the Signal-Seeker™ tools used to study them by scrolling through the information below.
Cytoskeleton, Inc. has a wide assortment of Signal-Seeker™tools and reagents. We've created a simple explanation video, as well as newsletters and citation spotlights to provide insight about these critical post translational modifications and the helpful tools used to investigate them. If you have any questions about a particular product or toolkit please send an email to cserve@cytoskeleton.com.
Learn More About Post Translational Modifications
Summary
Discover the exciting world of Post-Translational Modifications (PTMs). Learn about their role in biology, disease, and as therapeutic targets. Discover established and cutting-edge methods and approaches used to investigate PTMs. See real world examples where these tools were utilized to make ground-breaking PTM discoveries.
Chapters:
Chapter 1: PTMs: Functional Regulators of Disease (Click here)
Chapter 2: Proteoform Discovery and Validation Techniques for the Molecular Biologist (Click here)
Chapter 3: Signal-Seeker PTM Discovery Toolkits: Utilities and Applications (Click here)
Chapter 4: Mass Spectrometry and Post-Translational Modifications (Click here)
Chapter 5: PTM Functional Characterization and Beyond (Click here)
Download the complete eBook (Click here)
See How PTMs Regulate Disease Processes
Our most recent Signal-Seeker™ PTM writings can be found below. However Cytoskeleton has been writing about Post Translational Modifications for years, and that library of information can be found here
Leveraging SUMOylation To Regulate Immune Response
The small ubiquitin-like modifier 1 (SUMO1) was first identified in 19971 and since then, several isoforms (SUMO2, SUMO3, SUMO4, SUMO5), the SUMO enzymatic machinery (E1, E2, E3), and de-SUMOylases (SENPs) have been identified and characterized(reviewed in 2) (see Figure 1). Furthermore, it has been shown that this critical post-translational modification can selectively modify thousands of target proteins in a regulated fashion to control the protein’s localization, stability, and function; thereby, modulating critically important cellular processes like DNA repair, stress response, cellular trafficking, and many others(reviewed in 2). Thus, it is not surprising that dysregulation of SUMOylation has been linked to many diseases including cancer. There are many examples where dysregulation of SUMOylation acts on the cancer cell directly to augment its proliferation, migration, and metastasis (reviewed in 3) . Of equal importance, there is compelling evidence that SUMOylation facilitates cancer progression by modifying the tumor microenvironment and disrupting normal immune surveillance. In this newsletter, the effects of SUMOylation on the immune cells in both cancer and host immune responses are discussed.
Ubiquitination Is Key In The War With Bacteria
Ubiquitination is a well-studied post-translational modification (PTM) that regulates a multitude of cellular events through its well-established role of targeting proteins for degradation via the proteasome. More recently, the ubiquitin (Ub) machinery has been shown to play a key role in targeting organelles such as mitochondria and endoplasmic reticulum for recycling in cooperation with the autophagic machinery. However, the Ub system does not only regulate the host-cell’s protein turnover; rather, increasing evidence shows that it plays a key role in the cells defense against invading bacterial pathogens (reviewed in [1]) . In nearly all cases, ubiquitination of these targets occur through the classical E1, E2, and E3 enzyme cascade to attach Ub to key lysine residues on target proteins and mark them for degradation. Here we describe the unique ways the Ub system is deployed to defend the cell against invading bacterial pathogens, and how these pathogens have fought back to dismantle the ubiquitin system in a battle of survival.
Signal-Seeker™ Tools In Action - Citation Spotlights
Degradation Of CCNK/CDK12 Is A Druggable Vulnerability Of Colorectal Cancer
O2-Dependent Protein Internalization Underlies Astrocytic Sensing Of Acute Hypoxia By Restricting Multimodal TRPA1 Channel Responses
Novel therapies are needed to combat cancer cells that acquire resistance to current treatments, as well as, to find more efficacious drugs with defined mechanisms and better therapeutic windows. Dieter et al. sought to identify a novel treatment for colorectal cancer (CRC); utilizing an array of techniques and validation models they identified NCT02 as a novel therapeutic that specifically treated a subset of CRCs. To achieve their goal, an 80,000 small molecule library screen was tested against patient-derived CRC spheroids. After multiple rounds of validation and selective screening, 14 compounds were chosen for additional testing. These compounds were analyzed against eight different tumor spheroid cultures as well as primary fibroblasts, the result was NCT02 being identified as a suitable drug that targeted a subset of CRCs while lacking activity against primary fibroblasts. The group then utilized transcriptome analysis tools to identify the molecular pathways regulated by NCT02, which revealed several converging DNA damaging pathways as targets of this drug.
Oxygen, which is critical for ATP generation in aerobic organisms, is essential for life; conversely deprivation of oxygen, hypoxia, results in impaired cell signaling, energy crisis, and ultimately demise. Specific organs of the body have much higher consumption of O2 such as the central nervous system (CNS) which has high energy demands. Recently, Uchiyama et al. investigated the mechanisms by which neuronal cells regulate and respond to O2 deprivation and determined that a sensor cation channel transient receptor potential (TRP) A1 in pFRG/RTN astrocytes are critical for responding to hypoxic conditions. Interestingly, they determined that under normoxic conditions TRPA1 undergoes proline hydroxylation and internalization from the plasma membrane. Once internalized it is polyubiquitinated by the E3 ubiquitin ligase NEDD4-1 and targeted for degradation. Conversely, under hypoxic conditions the TRPA1 protein rapidly accumulates at the plasma membrane and is no longer ubiquitinated. This accumulation mediates calcium influx ....
Please visit our product pages for product specific citations
Ubiquitination Detection Kit - Acetyl-Lysine Detection Kit- Sumoylation 2/3 Detection Kit
Post-translational acetylation occurs on the epsilon amino group of lysine residues as a reversible and highly dynamic PTM that is known to be a key regulator in multiple cellular events, including chromatin structure, transcription, metabolism, signal transduction and cytoskeletal regulation.
Protein ubiquitination is a regulatory mechanism that controls protein:protein interactions, protein degradation, and spatial localization, which is mediated by chain specific poly-ubiquitination and/or mono-ubiquitination. Signal-Seeker™ ubiquitination tools have the unqiue ability to capture both mono- and poly-ubiquitination for any target protein.
SUMOylation is a dynamic and reversible process that plays pivotal roles in transcriptional regulation, chromatin remodeling, response to stress and regulation of mitosis. Signal-Seeker™ SUMOylation 1 products provide a simple and effective way to determine if your target protein is modified and regulated by this PTM.
SUMOylation 2/3 Tools Brochure
SUMOylation is a dynamic and reversible process that plays pivotal roles in transcriptional regulation, chromatin remodeling, response to stress and regulation of mitosis. Signal-Seeker™ SUMOylation 2/3 products provide a simple and effective way to determine if your target protein is modified and regulated by this PTM.
Phosphotyrosine Tools Brochure
Tyrosine phosphorylation, a reversible process, is a frequent post-translational modification of proteins and is crucial in mediating signal transduction in eukaryotic cells after exposure to cytokines and growth factors. Signal-Seeker™ phosphotyrosine products provide a comprehensive system to validate and study novel phosphotyrosine modifications for any target protein.
Have a technical question about our tools? Send us an email at tservice@cytoskeleton.com and our experts will anwser any question you may have!