5 years ago

Regulation Of Iron Homeostasis By SPAK-Dependent Modulation Of FBXL5 Stability

Wohlschlegel, A. A., Shenouda, M., D. N., Vashisht, Yao, C., Powers, J. A.
Intracellular iron homeostasis is regulated by a proteolytic switch whereby the E3 ubiquitin ligase FBXL5 targets iron regulatory proteins (IRPs) for ubiquitin-dependent degradation in iron-replete conditions while it is itself degraded during iron deficiency allowing IRPs to accumulate and regulate their downstream RNA targets. The cellular pathways that control FBXL5 degradation in low iron conditions are not well understood. Here, we report the identification of the STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) as a novel regulator of FBXL5 stability. We find that SPAK, a kinase previously implicated in osmotic stress regulation, regulates intracellular iron homeostasis through its physical association with FBXL5. This role is dependent on its kinase activity as overexpression of constitutively active SPAK increases FBXL5 poly-ubiquitination and degradation. Through this work, we have discovered a novel role for SPAK that extends beyond its well-established function in salt homeostasis and raises the possibility for signaling crosstalk between iron homeostatic and osmotic regulatory pathways.

Publisher URL: http://biorxiv.org/cgi/content/short/133777v1

DOI: 10.1101/133777

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.