Modulating Enzyme’s Activity and Specificity through Pre-Installed Posttranslational Modifications (PTMs) on Substrate: The Role of PTM-induced Substrate-Assisted Stimulation

20 March 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Understanding the underlying principles for crosstalk involving posttranslational modifications (PTMs) is of fundamental importance. In this article, we review some of previous results which indicated that pre-installed PTMs on nucleosome substrates (or nucleosome peptides) may stimulate the activity and change the specificity of histone modifying enzymes for the next PTMs. Discussions are also made on the results showing that ubiquitin (Ub) within the M1-diUb substrate could remodel the active site of OTULIN, a human deubiquitinase (DUB), and stimulate its activity. We term such stimulation effects as PTM-induced substrate-assisted stimulation (PTM-induced SAS) and propose that it could be one of the general strategies in PTM crosstalk and may provide a unique way to relay signals. It is suggested that although PTM-induced SAS seems to offer an attractive mechanism, detailed studies are still necessary to fully understand how the stimulations are created and translated into the increased activities and how widely it may occur in biological systems.


Posttranslational modification
Histone modifying enzymes
Substrate-assisted stimulation
Enzyme catalysis


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