Examples of post-translational modification in the following topics:
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- There are many examples of translational or post-translational modifications of proteins that arise in cancer.
- Modifications are found in cancer cells from the increased translation of a protein to changes in protein phosphorylation to alternative splice variants of a protein.
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- Posttranslational modification (PTM) is the chemical modification of a protein after its translation.
- This amino acid is usually taken off during post-translational modification.
- Non-standard amino acids that are found in proteins are formed by post-translational modification, which is modification after translation during protein synthesis.
- Another example is the formation of hypusine in the translation initiation factor EIF5A through modification of a lysine residue.
- Such modifications can also determine the localization of the protein.
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- Chemical modifications occur in response to external stimuli such as stress, the lack of nutrients, heat, or ultraviolet light exposure.
- These changes can alter protein function, epigenetic accessibility, transcription, mRNA stability, or translation; all resulting in changes in expression of various genes.
- Because proteins are involved in every stage of gene regulation, the phosphorylation of a protein (depending on the protein that is modified) can alter accessibility to the chromosome, can alter translation (by altering transcription factor binding or function), can change nuclear shuttling (by influencing modifications to the nuclear pore complex), can alter RNA stability (by binding or not binding to the RNA to regulate its stability), can modify translation (increase or decrease), or can change post-translational modifications (add or remove phosphates or other chemical modifications).
- Another example of chemical modifications affecting protein activity include the addition or removal of methyl groups.
- Methyl groups are added to proteins via the process of methylation; this is the most common form of post-translational modification.
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- To synthesize a protein, the processes of transcription (DNA to RNA) and translation (RNA to protein) occur almost simultaneously.
- The newly-synthesized RNA is then transported out of the nucleus into the cytoplasm where ribosomes translate the RNA into protein.
- The processes of transcription and translation are physically separated by the nuclear membrane; transcription occurs only within the nucleus, and translation occurs only outside the nucleus within the cytoplasm.
- Regulation may occur when the DNA is uncoiled and loosened from nucleosomes to bind transcription factors (epigenetics), when the RNA is transcribed (transcriptional level), when the RNA is processed and exported to the cytoplasm after it is transcribed (post-transcriptional level), when the RNA is translated into protein (translational level), or after the protein has been made (post-translational level).
- Further regulation may occur through post-translational modifications of proteins.
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- It is now known that mRNA is not always translated into protein.
- Not only does the translation from mRNA cause differences, but many proteins are also subjected to a wide variety of chemical modifications after translation which are critical to the protein's function such as phosphorylation, ubiquitination, methylation, acetylation, glycosylation, oxidation, and nitrosylation.
- Second, as mentioned above many proteins experience post-translational modifications that profoundly affect their activities.
- Third, many transcripts give rise to more than one protein through alternative splicing or alternative post-translational modifications.
- There are also antibodies specific to other modifications.
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- Other human proteins that are used as drugs require biological modifications that only the cells of mammals, such as cows, goats, and sheep, can provide.
- Genetic modifications introduced to a protein have many advantages over chemical modifications.
- The changes are introduced in 100% of the molecules with the exclusion of rare errors in gene transcription or translation.
- Bacteria did not develop sophisticated mechanisms for performing post-translational modifications that are present in higher organisms.
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- To synthesize a protein, the processes of transcription and translation occur almost simultaneously.
- The processes of transcription and translation are physically separated by the nuclear membrane: transcription occurs only within the nucleus, and translation occurs only outside the nucleus in the cytoplasm.
- Regulation may occur when the DNA is uncoiled and loosened from nucleosomes to bind transcription factors (epigenetic level); when the RNA is transcribed (transcriptional level); when the RNA is processed and exported to the cytoplasm after it is transcribed (post-transcriptional level); when the RNA is translated into protein (translational level); or after the protein has been made (post-translational level).
- Prokaryotic transcription and translation occur simultaneously in the cytoplasm; regulation occurs at the transcriptional level.
- Further regulation may occur through post-translational modifications of proteins.
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- Modifications, such as the overexpression of miRNAs, in the post-transcriptional control of a gene can result in cancer.
- Post-transcriptional regulation is the control of gene expression at the RNA level; therefore, between the transcription and the translation of the gene.
- After being produced, the stability and distribution of the different transcripts is regulated (post-transcriptional regulation) by means of RNA-binding proteins (RBP) that control the various steps and rates of the transcripts: events such as alternative splicing, nuclear degradation (exosome), processing, nuclear export (three alternative pathways), sequestration in DCP2-bodies for storage or degradation, and, ultimately, translation.
- Changes in the post-transcriptional control of a gene can result in cancer.
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- This can be the result of gene mutation or changes in gene regulation (epigenetic, transcription, post-transcription, translation, or post-translation).
- Changes in epigenetic regulation, transcription, RNA stability, protein translation, and post-translational control can be detected in cancer.
- Therefore, changes in histone acetylation (epigenetic modification that leads to gene silencing), activation of transcription factors by phosphorylation, increased RNA stability, increased translational control, and protein modification can all be detected at some point in various cancer cells.
- Scientists are working to understand the common changes that give rise to certain types of cancer or how a modification might be exploited to destroy a tumor cell.
- Overexpression of the oncogene can lead to uncontrolled cell growth because oncogenes can alter transcriptional activity, stability, or protein translation of another gene that directly or indirectly controls cell growth.
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- Transcription and translation in archaea resemble these processes in eukaryotes more than in bacteria.
- The proteins that archaea, bacteria and eukaryotes share form a common core of cell function, relating mostly to transcription, translation, and nucleotide metabolism.
- Transcription and translation in archaea resemble these processes in eukaryotes more than in bacteria, with the archaean RNA polymerase and ribosomes being very close to their equivalents in eukaryotes.
- Post-transcriptional modification is simpler than in eukaryotes, since most archaean genes lack introns, although there are many introns in their transfer RNA and ribosomal RNA genes, and introns may occur in a few protein-encoding genes.