Citrullination and the protein code: crosstalk between post-translational modifications in cancer
Koyo Harada1, Simon M Carr1, Amit Shrestha1
1Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
Summary
Protein arginine citrullination, mediated by peptidylarginine deiminases (PADs), impacts cell signaling and disease, particularly cancer. This review explores PAD functions, citrullination
Area of Science:
- Molecular Biology
- Epigenetics
- Cellular Signalling
Background:
- Post-translational modifications (PTMs) regulate crucial cellular processes.
- Protein arginine citrullination by peptidylarginine deiminases (PADs) is implicated in disease pathogenesis, especially cancer.
- The in vivo functions and mechanisms of PADs remain incompletely understood.
Approach:
- This review synthesizes current knowledge on PAD functions.
- It focuses on the role of citrullination in cancer biology.
- The review highlights the interplay between citrullination and other PTMs.
Key Points:
- PADs catalyze protein arginine citrullination, a PTM with significant roles in molecular and cell biology.
- Citrullination is an emerging druggable target for diseases, including cancer.
- Understanding the cross-talk between citrullination and other PTMs is crucial for elucidating downstream biological events.
Conclusions:
- Further research into PADs and citrullination is essential for understanding their physiological and pathological roles.
- Targeting PADs and citrullination pathways may offer novel therapeutic strategies for cancer.
- Elucidating the interplay of citrullination with other PTMs will advance our knowledge of cellular regulation.
Keywords:
cancercitrullinationmethylationpeptidylarginine deiminasepost-translational modificationsproteinMore Related Videos
Related Concept Videos
02:04Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
03:03mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
02:23Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
01:26Protein Modifications in the RER
5.2K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.2K
01:22PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
01:37Epigenetic Regulation
3.1K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.1K