Up increases the need for constant re-synthesis which ensures

Up to date, several authors reported the proteasomaldegradation of FIT. A combination of CHX and MG132 treatment initiallydemonstrated that FIT is degraded, which is pronounced under Fe deficiency (Meiser et al., 2011; Sivitz et al., 2011). It iscontroversially discussed why this turn-over control is needed and how this isregulated. It cannot be ruled out that the proteasome targets FIT independentlyfrom its activity status.

Besides, a large pool of inactive FIT could exist,from which FIT is recruited and subsequently activated by a yet unknownmechanism (Lingam et al., 2011). Thisstudy was supported by the finding, that smallest traces of active FIT aresufficient for downstream transcriptional control (Meiser et al., 2011).

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Another hypothesis suggests, that the degradation of active, but “exhausted”FIT forms increases the need for constant re-synthesis which ensuresaccumulation 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 FITprotein, since the protein can affect its own gene transcription (Jakoby et al., 2004; Wang et al., 2007).  Besides the fact that differential protein-proteininteractions might contribute to a selection between different activity levelsof FIT, post-translational modifications (PTMs) might be involved as well.

Thismight be needed in order to mediate the hetero-dimerization with otherproteins, for example subgroup Ib bHLH transcription factors, which are exclusivelyup-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). Inagreement with this hypothesis is the fact that the observed molecular weightof FIT is higher as predicted (Sivitz et al., 2011). This pointsout the possibility that FIT undergoes additional, yet undetected, PTMs whichmight have a regulatory impact on its activity.