Noncanonical retinoic acid signaling

Jennifer Nhieu, Yu Lung Lin, Li Na Wei

Research output: Chapter in Book/Report/Conference proceedingChapter

7 Scopus citations


All-trans retinoic acid (atRA) is the principle active metabolite of Vitamin A. atRA is well known to act through nuclear RA receptors (RARs) to regulate gene expression involved in a wide spectrum of biological processes such as growth, differentiation, and function. Recently, novel activities of atRA, independent of the action of RARs, have been increasingly reported and referred to as noncanonical activities. We have determined cellular retinoic acid binding protein 1 (CRABP1) as the primary mediator of the noncanonical activities of atRA. At the molecular level, atRA binds CRABP1, which then immediately acts as an adaptor in the formation of specific signaling scaffolds to rapidly modulate downstream signaling pathways in a cell context-dependent manner. The first established CRABP1-atRA activity is to rapidly dampen the activation of the mitogen-activated protein kinase (MAPK) cascade in response to growth factor stimulation, thereby suppressing cell cycle progression of stem cells. The second established activity is to rapidly reduce Ca2 +/calmodulin dependent kinase II (CaMKII) activity in differentiated cells such as cardiomyocyte in response to β-adrenergic stimulation. This chapter describes in vivo and in vitro experimental systems and methodologies appropriate for determining the noncanonical activities of atRA that are mediated by CRABP1 and cell context dependent.

Original languageEnglish (US)
Title of host publicationRetinoid Signaling Pathways
EditorsEhmke Pohl
PublisherAcademic Press Inc.
Number of pages21
ISBN (Print)9780128201442
StatePublished - 2020

Publication series

NameMethods in enzymology
PublisherAcademic Press Inc.
ISSN (Print)0076-6879

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.


  • CRABP1
  • CaMKII
  • Noncanonical
  • RAF
  • Retinoic acid


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