Up increases the need for constant re-synthesis which ensures

Up to date, several authors reported the proteasomal
degradation of FIT. A combination of CHX and MG132 treatment initially
demonstrated that FIT is degraded, which is pronounced under Fe deficiency (Meiser et al., 2011; Sivitz et al., 2011). It is
controversially discussed why this turn-over control is needed and how this is
regulated. It cannot be ruled out that the proteasome targets FIT independently
from its activity status. Besides, a large pool of inactive FIT could exist,
from which FIT is recruited and subsequently activated by a yet unknown
mechanism (Lingam et al., 2011). This
study was supported by the finding, that smallest traces of active FIT are
sufficient for downstream transcriptional control (Meiser et al., 2011).
Another hypothesis suggests, that the degradation of active, but “exhausted”
FIT forms increases the need for constant re-synthesis which ensures
accumulation of “fresh” forms that mediate downstream gene expression (Sivitz et al., 2011). Thus,
it might be that the Fe uptake response is regulated by the stability of FIT
protein, since the protein can affect its own gene transcription (Jakoby et al., 2004; Wang et al., 2007).

 

Besides the fact that differential protein-protein
interactions might contribute to a selection between different activity levels
of FIT, post-translational modifications (PTMs) might be involved as well. This
might be needed in order to mediate the hetero-dimerization with other
proteins, for example subgroup Ib bHLH transcription factors, which are exclusively
up-regulated under Fe limiting conditions and are needed for FIT target gene expressionR1 
(Wang et al., 2007; Yuan et al., 2008; Mai et al.,
2015; Mai et al., 2016; Naranjo-Arcos et al., 2017). In
agreement with this hypothesis is the fact that the observed molecular weight
of FIT is higher as predicted (Sivitz et al., 2011). This points
out the possibility that FIT undergoes additional, yet undetected, PTMs which
might have a regulatory impact on its activity.

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