Use the following passage to answer questions: Very few proteins carry out their functions in the cell as unmodified folded polypeptides. Nearly all proteins undergo post-translational modifications (PTMs) in various cellular compartments, including the cytosol, Golgi apparatus, and endoplasmic reticulum. One common modification type is proteolytic cleavage, which involves irreversible processing of a polypeptide by proteases. Another major category of PTMs is covalent modification of specific amino acid residues. Among the many examples of these modifications are phosphorylation,... Show more Use the following passage to answer questions: Very few proteins carry out their functions in the cell as unmodified folded polypeptides. Nearly all proteins undergo post-translational modifications (PTMs) in various cellular compartments, including the cytosol, Golgi apparatus, and endoplasmic reticulum. One common modification type is proteolytic cleavage, which involves irreversible processing of a polypeptide by proteases. Another major category of PTMs is covalent modification of specific amino acid residues. Among the many examples of these modifications are phosphorylation, acetylation, methylation, and glycosylation. There is evidence that every amino acid residue can be decorated with one or more of these modification groups. The specificity of this type of PTM is partially determined by the pattern of amino acids surrounding the target residue. Because PTMs affect myriad properties of proteins, including stability, localization, and interaction with other proteins, there has been intense effort in biological research to characterize the PTMs of individual proteins and protein populations in the cell. The influence of PTMs on protein function is illustrated by the example of p53, a canonical tumor suppressor protein. The levels of p53 in mammalian cells are tightly regulated by a modification called ubiquitination. Under normal conditions, the addition of multiple ubiquitin groups to p53 results in the sequestration of the protein into the 26S proteasome complex and its consequent clearance from the cell. However, when the cell encounters stress, such as DNA damage or the activation of an oncogene, another pattern of PTM confers the stabilization of p53. Under these conditions, ubiquitination is suppressed, and p53 is instead acetylated and phosphorylated; both of these modifications stabilize the protein. P53 primarily functions as a transcriptional activator or repressor, and its target genes are involved in cell cycle arrest, apoptosis, and DNA repair. It accomplishes these functions in homotetrameric complexes, and phosphorylation of p53 has additionally been demonstrated to increase the complex's sequence-specific binding to DNA. PTMs are dynamic; phosphorylation, which often occurs in the cytosol, is controlled by kinase enzymes, whereas removal of phosphate groups is carried out by another set of enzymes called phosphatases. Similarly, while histone acetyltransferases add acetyl groups to p53, histone deacetylases remove them. P53 has also been shown to undergo additional PTMs: neddylation, which could repress its transactivator activity; sumoylation, which could act like ubiquitination; glycosylation; and ribosylation. The importance of p53 in cancer formation is illustrated by the fact that more than 20,000 mutations in the protein have been found in various cancer types. Many mutations lie in the p53 DNA binding domain and give rise to oncogenic properties. Additionally, mutations often result in increased phosphorylation and acetylation and, thus, stabilization of these oncogenic forms of p53. Show less
Use the following passage to answer questions:
Very few proteins carry out their functions in the cell as unmodified folded polypeptides. Nearly all proteins undergo post-translational modifications (PTMs) in various cellular compartments, including the cytosol, Golgi apparatus, and endoplasmic reticulum. One common modification type is proteolytic cleavage, which involves irreversible processing of a polypeptide by proteases. Another major category of PTMs is covalent modification of specific amino acid residues. Among the many examples of these modifications are phosphorylation, acetylation, methylation, and glycosylation. There is evidence that every amino acid residue can be decorated with one or more of these modification groups.
The specificity of this type of PTM is partially determined by the pattern of amino acids surrounding the target residue. Because PTMs affect myriad properties of proteins, including stability, localization, and interaction with other proteins, there has been intense effort in biological research to characterize the PTMs of individual proteins and protein populations in the cell. The influence of PTMs on protein function is illustrated by the example of p53, a canonical tumor suppressor protein. The levels of p53 in mammalian cells are tightly regulated by a modification called ubiquitination. Under normal conditions, the addition of multiple ubiquitin groups to p53 results in the sequestration of the protein into the 26S proteasome complex and its consequent clearance from the cell. However, when the cell encounters stress, such as DNA damage or the activation of an oncogene, another pattern of PTM confers the stabilization of p53. Under these conditions, ubiquitination is suppressed, and p53 is instead acetylated and phosphorylated; both of these modifications stabilize the protein. P53 primarily functions as a transcriptional activator or repressor, and its target genes are involved in cell cycle arrest, apoptosis, and DNA repair. It accomplishes these functions in homotetrameric complexes, and phosphorylation of p53 has additionally been demonstrated to increase the complex's sequence-specific binding to DNA. PTMs are dynamic; phosphorylation, which often occurs in the cytosol, is controlled by kinase enzymes, whereas removal of phosphate groups is carried out by another set of enzymes called phosphatases.
Similarly, while histone acetyltransferases add acetyl groups to p53, histone deacetylases remove them. P53 has also been shown to undergo additional PTMs: neddylation, which could repress its transactivator activity; sumoylation, which could act like ubiquitination; glycosylation; and ribosylation. The importance of p53 in cancer formation is illustrated by the fact that more than 20,000 mutations in the protein have been found in various cancer types. Many mutations lie in the p53 DNA binding domain and give rise to oncogenic properties. Additionally, mutations often result in increased phosphorylation and acetylation and, thus, stabilization of these oncogenic forms of p53.
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