Pleiotropic functions of biliverdin reductase: cellular signaling and generation of cytoprotective and cytotoxic bilirubin

Jaime Kapitulnik*, Mahin D. Maines

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

161 Scopus citations

Abstract

Degradation of heme requires its conversion to biliverdin (BV) by heme oxygenase, followed by reduction of BV to the free-radical quencher bilirubin (BR) by biliverdin reductase (BVR). It is now recognized that human BVR (hBVR) is a dual-specificity kinase (Ser/Thr and Tyr) upstream activator of the insulin/insulin growth factor-1 (IGF-1) and mitogen-activated protein kinase (MAPK) signaling pathways. hBVR is also a basic-leucine-zipper (bZip) DNA/chromatin-binding transcription factor, an activator and anchor protein for translocation of protein kinase C βII and ζ isozymes within cell compartments, and a kinase kinase for their activation. hBVR is essential for MAPK-extracellular signal-regulated kinase (ERK)1/2 (MEK)-eukaryotic-like protein kinase (Elk) signaling and has been identified as the cytoplasm-nuclear heme transporter of ERK1/2 and hematin, the key components of stress-responsive gene expression. Here, we discuss the recently uncovered functions of hBVR in cell signaling and regulation of gene expression, and the role of BR in cellular signaling, cytoprotection and cytotoxicity.

Original languageEnglish
Pages (from-to)129-137
Number of pages9
JournalTrends in Pharmacological Sciences
Volume30
Issue number3
DOIs
StatePublished - Mar 2009

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