Chronicle of a discovery: the retinoic acid receptor

Giguère, Vincent; Evans, Ronald M.

doi:10.1530/jme-22-0117

Cited by 15 publications

(11 citation statements)

References 101 publications

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“…NR degradation is critical for the activity of the endogenous RARA agonist, all- trans RA (ATRA), in the treatment of acute promyelocytic leukemia (APML), driven by a fusion of the RARA and the promyelocytic protein ( PML ) genes. 10 Cure of APML requires both the activation of transcriptional programs by PML-RARA and degradation of the fusion protein in response to ATRA and arsenic trioxide (ATO). 11 – 15 Selective ER degraders (SERDs), such as fulvestrant, are widely used in the treatment of breast cancer, and novel therapies that induce degradation of ER are in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability

Tsai

Aguirre

et al. 2023

Molecular Cell

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Section: Introductionmentioning

confidence: 99%

UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability

Tsai

Aguirre

et al. 2023

Molecular Cell

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“…Initially, a receptor which could bind retinoic acid (RAR) and with the capacity to function as a ligand-inducible transcription factor was described 1987 independently by Pierre Chambon and Ronald Evans ( 79 , 80 ). Recently, the background for the discoveries have been described in two fascinating papers by each group ( 25 , 26 ). Shortly afterwards, Pierre Chambon and Magnus Phfahl cloned a second RAR ( 81 , 82 ).…”

Section: Vitamin a Receptor Signalingmentioning

confidence: 99%

Vitamin A – discovery, metabolism, receptor signaling and effects on bone mass and fracture susceptibility

Lerner

2024

Front. Endocrinol.

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The first evidence of the existence of vitamin A was the observation 1881 that a substance present in small amounts in milk was necessary for normal development and life. It was not until more than 100 years later that it was understood that vitamin A acts as a hormone through nuclear receptors. Unlike classical hormones, vitamin A cannot be synthesized by the body but needs to be supplied by the food as retinyl esters in animal products and ß-carotene in vegetables and fruits. Globally, vitamin A deficiency is a huge health problem, but in the industrialized world excess of vitamin A has been suggested to be a risk factor for secondary osteoporosis and enhanced susceptibility to fractures. Preclinical studies unequivocally have shown that increased amounts of vitamin A cause decreased cortical bone mass and weaker bones due to enhanced periosteal bone resorption. Initial clinical studies demonstrated a negative association between intake of vitamin A, as well as serum levels of vitamin A, and bone mass and fracture susceptibility. In some studies, these observations have been confirmed, but in other studies no such associations have been observed. One meta-analysis found that both low and high serum levels of vitamin A were associated with increased relative risk of hip fractures. Another meta-analysis also found that low levels of serum vitamin A increased the risk for hip fracture but could not find any association with high serum levels of vitamin A and hip fracture. It is apparent that more clinical studies, including large numbers of incident fractures, are needed to determine which levels of vitamin A that are harmful or beneficial for bone mass and fracture. It is the aim of the present review to describe how vitamin A was discovered and how vitamin A is absorbed, metabolized and is acting as a ligand for nuclear receptors. The effects by vitamin A in preclinical studies are summarized and the clinical investigations studying the effect by vitamin A on bone mass and fracture susceptibility are discussed in detail.

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“…Two families of nuclear receptors mediate the classical biological effects of retinoids, retinoic acid receptors (RARs), and retinoic X receptors (RXRs) ( 25 , 28 , 29 ). Three isotypes (α, β, and γ), encoded by separate genes, make up each family, and these receptor subtypes are present in different isoforms due to alternate splicing and different promoter usage.…”

Section: Physiologymentioning

confidence: 99%

Vitamin A – a scoping review for Nordic nutrition Recommendations 2023

Olsen,

Lerner

2023

Food & Nutrition Research

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Vitamin A refers to a group of fat-soluble compounds with retinol activity, including all- trans retinol and pro-vitamin A carotenoids. Bioactive compounds include retinal and all- trans retinoic acid with important functions in vision, immune function, growth, and development. The literature search that was performed for the current scoping review yielded a total of seven publications relevant to setting the recommended daily intake for vitamin A. In total, six publications assessed the relationship of serum retinol and/or dietary vitamin A intake with fracture risk ( n = 2), cancer ( n = 3), and deficiency after bariatric surgery ( n = 1). One additional report by the European Food Safety Administration (EFSA) with updated average requirements was included. The outcomes-based systematic reviews and meta-analyses showed positive associations for vitamin A intake and serum retinol with risk of hip fracture. Weak or inconclusive associations were observed for cancer or obesity. One publication by EFSA with updated estimated average requirements and population reference intakes for dietary vitamin A intakes was published in 2015. The EFSA recommendations and estimated average requirements are based on a European reference population, with body weights derived from an assumed body mass index of 22, which might be too low and not representative of the Nordic and Baltic populations, and consequently resulting in lower estimated average requirements and recommendations. In conclusion, there were limited new outcomes-based data for vitamin A and health outcomes.

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Chronicle of a discovery: the retinoic acid receptor

Cited by 15 publications

References 101 publications

UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability

UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability

Vitamin A – discovery, metabolism, receptor signaling and effects on bone mass and fracture susceptibility

Vitamin A – a scoping review for Nordic nutrition Recommendations 2023

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