Distinct Roles for Cellular Retinoic Acid-binding Proteins I and II in Regulating Signaling by Retinoic Acid

Dong, Diane; Ruuska, Sarah; Levinthal, David J.; Noy, Noa

doi:10.1074/jbc.274.34.23695

Cited by 320 publications

(303 citation statements)

References 24 publications

Supporting

Mentioning

280

Contrasting

Unclassified

Order By: Relevance

“…constant K d is in the 0.1Ϫ0.2 nmol/L range) 43,44 than the binding affinity of FABP5 and PPAR␤ for RA (K d in the 10 to 50 nmol/L range). 45 When highly enriched in the cytoplasm, FABP5 can compete with CRABP2 for RA ligand binding, thus reducing the availability of free RA directed toward the RA-CRABP2-RAR pathway.…”

Section: Discussionmentioning

confidence: 91%

Association of FABP5 Expression With Poor Survival in Triple-Negative Breast Cancer

Liu

Graham

Glubrecht

et al. 2011

The American Journal of Pathology

143

124

View full text Add to dashboard Cite

Recent studies using animal models suggest that expression of FABP5 drives the stimulation of cell growth observed in estrogen receptor (ER)-negative breast cancer cells on exposure to retinoic acid (RA). The purpose of this study was to investigate the clinicopathological significance of FABP5 in breast cancer and to evaluate FABP5 as a prognostic marker and a possible novel therapeutic target in breast cancer. Gene expression microarray analysis revealed a significant correlation between elevated FABP5 RNA levels and ER/ progesterone receptor (PR)-negative status, high tumor grade, and poor prognosis. Tissue microarray analysis demonstrated similar correlations with cytoplasmic FABP5 protein. Based on multivariate proportional regression analysis, cytoplasmic FABP5 is a significant and independent prognostic marker of overall survival and recurrence-free survival in breast cancer. The effects of FABP5 on tumor growth appear to be mediated primarily through cytoplasmic FABP, because no correlation was found between nuclear FABP5 and ER/PRnegative status, recurrence, and survival. FABP5 knockdown in breast cancer cell lines demonstrates a correlation between FABP5 levels and growth response to RA. We propose a model whereby growth-promoting FABP5 competes with growth-inhibiting CRABP2 for RA, with retention of RA in the cytoplasm by FABP5 preventing the inhibition of tumor growth. (Am J Pathol

show abstract

Section: Discussionmentioning

confidence: 91%

Association of FABP5 Expression With Poor Survival in Triple-Negative Breast Cancer

Liu

Graham

Glubrecht

et al. 2011

The American Journal of Pathology

143

124

View full text Add to dashboard Cite

show abstract

“…iLBPs bind a range of molecules, including lipids, vitamins, and other poorly water-soluble ligands (7,8), and can facilitate the cellular and nuclear transport of endogenous PPAR activators. For example, FABP1 expression increases fatty acid delivery to the nucleus (9 -11) and enhances ligandmediated transactivation of PPAR␣ in COS-7 and HepG2 cells (12); cellular retinoic acid-binding protein II translocates to the nucleus on binding retinoic acid, associates directly with the retinoic acid receptor, and thereby facilitates delivery of retinoic acid to its receptor (13)(14)(15); adipocyte-fatty acid-binding protein (A-FABP or FABP4) binds the PPAR␥ agonist troglitazone, promoting nuclear localization and PPAR␥ activation. Although FABP4 can bind agonists for PPAR␣, PPAR␤/␦, and PPAR␥, only PPAR␥ agonists stimulate nuclear localization of FABP4 (16).…”

mentioning

confidence: 99%

Fatty Acid-binding Proteins 1 and 2 Differentially Modulate the Activation of Peroxisome Proliferator-activated Receptor α in a Ligand-selective Manner

Hughes

Liu

Halls³

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Fatty acid-binding proteins (FABPs) chaperone intracellular transport of lipophilic ligands. Results: FABP1 and FABP2 differentially promote drug activation of peroxisome proliferator-activated receptor ␣ (PPAR␣) via ligand-dependent protein-protein interactions. Conclusion: Drug activation of PPAR␣ is regulated by the presence of different FABPs. Significance: FABPs may act in a tissue-specific manner to enhance the selectivity of PPAR␣ agonists.

show abstract

“…CRABP2 and FABP5 are cytosolic in the absence of their ligand, but upon binding of RA, they undergo a conformational change that activates their nuclear localization signals and results in their mobilization to the nucleus (5)(6)(7)(8). In the nucleus, these binding proteins associate with their cognate receptors to form a complex through which RA is directly "channeled" to the receptor (9). CRABP2 and FABP5 thus markedly enhance the transcriptional activities of RAR and PPAR␤/␦, respectively (3,5,7,10,11).…”

mentioning

confidence: 99%

Cellular Retinoic Acid-binding Protein 2 Inhibits Tumor Growth by Two Distinct Mechanisms

Vreeland

Levi

Zhang

et al. 2014

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: CRABP2 delivers RA to its cognate nuclear receptor RAR and regulates gene expression by cooperating with HuR in stabilizing mRNAs. Results: In conjunction with HuR, CRABP2 regulates the expression of multiple cancer-related genes and suppresses tumor growth. Conclusion:The anticarcinogenic activities of CRABP2 are mediated by both HuR and RAR.Significance: The data demonstrate a novel mechanism through which CRABP2 inhibits tumorigenesis.

show abstract

Distinct Roles for Cellular Retinoic Acid-binding Proteins I and II in Regulating Signaling by Retinoic Acid

Cited by 320 publications

References 24 publications

Association of FABP5 Expression With Poor Survival in Triple-Negative Breast Cancer

Association of FABP5 Expression With Poor Survival in Triple-Negative Breast Cancer

Fatty Acid-binding Proteins 1 and 2 Differentially Modulate the Activation of Peroxisome Proliferator-activated Receptor α in a Ligand-selective Manner

Cellular Retinoic Acid-binding Protein 2 Inhibits Tumor Growth by Two Distinct Mechanisms

Contact Info

Product

Resources

About