ASK1 (apoptosis signal-regulating kinase 1)
is a member of MAPKKK protein family, which directs cell towards inflammation
or apoptosis by means of either p38 or JNK signalling pathway [1, 2]. ASK1
dysregulation has been associated with cardiovascular , tumour  and
neurodegenerative  diseases and ASK1 thus represents a prospective target
for therapeutic intervention. ASK1 regulation involves both oligomerization and
interaction with multiple binding partners. To better understand the principle
of ASK1 activation, we investigated the oligomeric behaviour of the N-terminal
part under different redox conditions. Our results revealed that the N-terminal
part of ASK1 forms dimers in solution and that this dimerization is affected by
redox conditions. Moreover, we also identified regions that form the
dimerization interface of the N-terminal part of ASK1. In addition, our data
suggest that the interaction between ASK1 and its inhibitor thioredoxin is
considerably weaker in strong reducing conditions. Altogether, our findings
provide new insights into the mechanism of ASK1 inhibition by TRX.
This work was supported by the Czech Science Foundation (project 19-00121S) and the Grant Agency of Charles University (Grant No. 1160120).