MassIVE MSV000083739

Partial Public PXD013697

Oxygen-dependent interaction between FBXL5 and CIA targeting complex regulates iron homeostasis

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Description

The iron sensing protein FBXL5 is the substrate adaptor for a SKP1-CUL1-RBX1 E3 ubiquitin ligase complex that regulates the degradation of iron regulatory proteins (IRPs). Here we describe a mechanism of FBXL5 regulation involving its interaction with the cytosolic Fe-S cluster assembly (CIA) targeting complex comprised of MMS19, FAM96B, and CIAO1. We demonstrate that the CIA targeting complex promotes the ability of FBXL5 to degrade IRPs. In addition, the FBXL5-CIA targeting complex interaction is regulated by oxygen tension displaying a robust association in 21% O2 that is severely diminished in 1% O2 and contributes to O2-dependent regulation of IRP degradation. Together, these data identify a novel oxygen-dependent signaling axis that links IRP-dependent iron homeostasis with the Fe-S cluster assembly machinery. [doi:10.25345/C5M050] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: FBXL5 ; IRP ; MMS19 ; FAM96B ; CIAO1 ; CIA Targeting Complex ; Iron Homeostasis ; Hypoxia ; Poly-ubiquitination ; Iron Sensor ; CIA Targeting Complex Binding Domain

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Principal Investigators:
(in alphabetical order) 		James A. Wohlschlegel, University of California, Los Angeles, United States
Submitting User: wbarshop
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