Cellular retinoic acid binding protein I mediates rapid non-canonical activation of ERK1/2 by all-trans retinoic acid

Shawna D. Persaud, Yi Wei Lin, Cheng Ying Wu, Hiroyuki Kagechika, Li Na Wei*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

56 Scopus citations

Abstract

All-trans retinoic acid (atRA), one of the active ingredients of vitamin A, exerts canonical activities to regulate gene expression mediated by nuclear RA receptors (RARs). AtRA could also elicit certain non-canonical activities including, mostly, rapid activation of extracellular signal regulated kinase 1/2 (ERK1/2); but the mechanism was unclear. In this study, we have found that cellular retinoic acid binding protein I (CRABPI) mediates the non-canonical, RAR- and membrane signal-independent activation of ERK1/2 by atRA in various cellular backgrounds. In the context of embryonic stem cells (ESCs), atRA/CRABPI-dependent ERK1/2 activation rapidly affects ESC cell cycle, specifically to expand the G1 phase. This is mediated by ERK stimulation resulting in dephosphorylation of nuclear p27, which elevates nuclear p27 protein levels to block G1 progression to S phase. This is the first study to identify CRABPI as the mediator for non-canonical activation of ERK1/2 by atRA, and demonstrate a new functional role for CRABPI in modulating ESC cell cycle progression.

Original languageEnglish
Pages (from-to)19-25
Number of pages7
JournalCellular Signalling
Volume25
Issue number1
DOIs
StatePublished - 01 2013
Externally publishedYes

Keywords

  • CRABPI
  • Cell cycle
  • ERK
  • P27
  • Retinoic acid

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