Retinoic Acid
Hormones acting through Nuclear Receptors

DEFINITION

Retinoic acid is a metabolite of vitamin A (retinol) that mediates part of the functions of vitamin A required for growth and development.

The more active forms are all-trans-RA and 7-cis-RA

SYNTHESIS AND TURNOVER

The main enzymes involved in RA metabolism are

• the alcohol dehydrogenase ALDH1 (AL1A1_HUMAN, Retinal dehydrogenase 1) e ALDH2 (ALDH2_HUMAN, Aldehyde dehydrogenase, mitochondrial)
• the cytochrome P450 Cyp26 whose main function is to degrade endogenous all-trans retinoic acid (Retinoid metabolism: a balancing act, 2002)

Kegg's Pathways

Autocrine and/or paracrine effects

Retinoic acid in the development, regeneration and maintenance of the nervous system, 2007

Retinoic acid in development: towards an integrated view, 2008

CELLULAR FUNCTIONS

cellular localization,

Vi sono due isomeri dell’RA biologicamente attivi: il trans-RA e il 9-cis-RA. (more info) L’RA si lega a due proteine citosoliche CRABP I e CRABP II. La prima è espressa ubiquitariamente mentre la seconda quasi esclusivamente a livello cutaneo.
Il complesso RA-CRBP trasloca nel nucleo e lega il retinoid-dependent nuclear receptor; questo recettore esiste in due forme: RAR e RXR entrambe appartenenti alla famiglia dei recettori nucleari per gli ormoni e in grado di agire come fattori di trascrizione.

biological function

• Cell signaling pathway

REGULATION

DIAGNOSTIC USE

Effect of 9-cis-Retinoic Acid on Growth and RXR Expression in Human Breast Cancer Cells, 1995

• Our results show that: (1) the growth of ER+/RA-sensitive breast cancer cells is inhibited by treatment with 9-cis-RA by blocking entry into S phase; (2) both ER+/RA-sensitive and ER-/RA-resistant breast cancer cell lines express RXR-α and RXR-β mRNAs but not RXR-γ however, levels of these transcripts did not correlate with the RA response; and (3) levels of RXR-α and RXR-β mRNA were not significantly altered following treatment with either all-trans-RA or 9-cis-RA. These results suggest that the mechanism responsible for the retinoid sensitivity of breast cancer cells does not involve transcriptional modulation of the RXRs by RA.