p53 regulation by ubiquitin and ubiquitin-like modifications

Wang, Ying; Zhang, Chenlu; Wang, Jiabao; Liu, Jiang

doi:10.1007/s42764-022-00067-0

Cited by 2 publications

(1 citation statement)

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“…In particular, dimerisation occurs co-translationally on the polysome, whereas tetramerisation is a posttranslational event that takes place in the nucleus [ 14 , 15 ]. Appropriate subcellular localisation is modulated by specific sequences within the C -terminal region [ 16 , 17 ]. In particular, there are three nuclear localization sequences (NLSs) (residues 316–325, 369–375 and 379–384) and a nuclear exporting sequence (NES) (residues 340–351), the latter being buried when the protein is in its tetrameric form [ 18 ] but accessible in the monomeric or dimeric forms.…”

Section: Introductionmentioning

confidence: 99%

How Do Cancer-Related Mutations Affect the Oligomerisation State of the p53 Tetramerisation Domain?

Nicolini

Todorovski

Puig

et al. 2023

CIMB

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Tumour suppressor p53 plays a key role in the development of cancer and has therefore been widely studied in recent decades. While it is well known that p53 is biologically active as a tetramer, the tetramerisation mechanism is still not completely understood. p53 is mutated in nearly 50% of cancers, and mutations can alter the oligomeric state of the protein, having an impact on the biological function of the protein and on cell fate decisions. Here, we describe the effects of a number of representative cancer-related mutations on tetramerisation domain (TD) oligomerisation defining a peptide length that permits having a folded and structured domain, thus avoiding the effect of the flanking regions and the net charges at the N- and C-terminus. These peptides have been studied under different experimental conditions. We have applied a variety of techniques, including circular dichroism (CD), native mass spectrometry (MS) and high-field solution NMR. Native MS allows us to detect the native state of complexes maintaining the peptide complexes intact in the gas phase; the secondary and quaternary structures were analysed in solution by NMR, and the oligomeric forms were assigned by diffusion NMR experiments. A significant destabilising effect and a variable monomer population were observed for all the mutants studied.

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