Related Experiment Video
Updated: Oct 27, 2025
Genome-wide Analysis of Histone Modifications Distribution using the Chromatin Immunoprecipitation Sequencing Method in Magnaporthe oryzae
Published on: June 2, 2021
The bZIP Transcription Factor HapX Is Post-Translationally Regulated to Control Iron Homeostasis in Aspergillus
Manuel Sánchez López-Berges1, Mareike Thea Scheven2,3, Peter Hortschansky2
1Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Abstract:
The airborne fungus Aspergillus fumigatus causes opportunistic infections in humans with high mortality rates in immunocompromised patients. Previous work established that the bZIP transcription factor HapX is essential for virulence via adaptation to iron limitation by repressing iron-consuming pathways and activating iron acquisition mechanisms. Moreover, HapX was shown to be essential for transcriptional activation of vacuolar iron storage and iron-dependent pathways in response to iron availability. Here, we demonstrate that HapX has a very short half-life during iron starvation, which is further decreased in response to iron, while siderophore biosynthetic enzymes are very stable. We identified Fbx22 and SumO as HapX interactors and, in agreement, HapX post-translational modifications including ubiquitination of lysine161, sumoylation of lysine242 and phosphorylation of threonine319. All three modifications were enriched in the immediate adaptation from iron-limiting to iron-replete conditions. Interfering with these post-translational modifications, either by point mutations or by inactivation, of Fbx22 or SumO, altered HapX degradation, heme biosynthesis and iron resistance to different extents. Consistent with the need to precisely regulate HapX protein levels, overexpression of hapX caused significant growth defects under iron sufficiency. Taken together, our results indicate that post-translational regulation of HapX is important to control iron homeostasis in A. fumigatus.
Insights
Post-translational modifications regulate the stability of HapX, a key virulence factor in Aspergillus fumigatus. This regulation is crucial for controlling iron homeostasis and preventing detrimental growth under iron sufficiency.
Area of Science:
- Medical Mycology
- Molecular Biology
- Biochemistry
Background:
- * *Aspergillus fumigatus* is an airborne fungus causing life-threatening infections in immunocompromised individuals.
- * The transcription factor HapX is vital for fungal virulence, mediating adaptation to iron limitation.
- * HapX controls iron consumption, acquisition, and storage pathways in response to iron availability.
Purpose of the Study:
- * To investigate the post-translational regulation of HapX stability and its role in iron homeostasis.
- * To identify factors and modifications affecting HapX levels during iron fluctuations.
- * To understand the impact of altered HapX regulation on fungal growth and virulence.
Main Methods:
- * Measurement of HapX half-life under varying iron conditions.
- * Identification of HapX interacting proteins (Fbx22, SumO) and post-translational modifications (ubiquitination, sumoylation, phosphorylation).
- * Analysis of the effects of interfering with these modifications on HapX degradation, heme biosynthesis, and iron resistance.
Main Results:
- * HapX exhibits a short half-life, further decreased upon iron addition, while siderophore enzymes remain stable.
- * Fbx22 and SumO were identified as interactors, with specific lysine and threonine residues on HapX undergoing modification.
- * Interference with these modifications or interactors altered HapX degradation, heme synthesis, and iron resistance.
- * Overexpression of *hapX* led to growth defects under iron-replete conditions.
Conclusions:
- * Post-translational modifications, including ubiquitination, sumoylation, and phosphorylation, precisely regulate HapX protein levels.
- * This regulation is critical for managing iron homeostasis in *A. fumigatus* during changing iron availability.
- * Precise control of HapX is essential, as its overexpression is detrimental under iron sufficiency.
Related Concept Videos
01:17Gene Regulation During Sporulation
02:42Transcription Attenuation in Prokaryotes
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
02:41Chromatin Structure Regulates pre-mRNA Processing
The chromatin structure, especially...
01:23Regulation of Expression at Multiple Steps
01:29Translational Regulation
01:30Other Stress Responses in Bacteria