Home Health Analysis of Protein Post-Translational Modifications by Mass Spectrometry
Biological Functions of Ub and SUMO
These two PTMs are highly regulated and can target a protein and assemble a monomodification or assemble more complex polymeric modifications consisting of branched and mixed chains comprising different lengths and linkages. For example, the process of ubiquitination can involve the targeting of a protein for monomodification with subsequent extension by the covalent addition of other ubiquitin proteins to the e-amino group of one of ubiquitin's
seven internal lysines (Lys 6, 11, 27, 29, 33, 48, and 63) or the a-amino group of its N-terminal methionine [15, 16]. The type of ubiquitin chain assembly on a modified protein directly impacts the protein-specific biological function within the cell. For example, modification of a protein by polyubiquitination chain assembly through the internal lysine 48-amino-acid residues of ubiquitin results in the protein being targeted for degradation in the 26S proteosome complex . Similarly, these different types of chain assemblies impact the specific biological function of the SUMOylated proteins [18, 19].
These two PTMs can be involved in a multitude of important and diverse biological functions: (i) independently, such as in protein endocytosis in the case of ubiquitination [20, 21] and transcriptional activity in the case of SUMOylation [22, 23]; (ii) in combination with each other, known as cross talk, such as in DNA damage, replication, and repair [24-26]; and (iii) cross talk with other PTMs, for example, cross talk between ubiquitination and phosphorylation such as in regulation of E3 ligase activity  and cross talk between acetylation and SUMOylation in regulating p53-dependent gene transcription by the promotion and inhibition of p53 binding to DNA and chromatin . Dysregulation of these ubiquitination and SUMOylation pathways has a substantial impact on the progression of a number of disease states including a number of cancers [29, 30] and neurodegenerative diseases [31, 32].
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