Formation of Arabidopsis Cryptochrome 2 Photobodies in Mammalian Nuclei

Ozkan-Dagliyan, Irem; Chiou, Yi Ying; Rui, Yong; Hassan, Bachar H.; Öztürk, Nuri; Sancar, Aziz

doi:10.1074/jbc.m113.493361

Cited by 38 publications

(23 citation statements)

References 31 publications

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“…In view of these observations and in continuation of our research studies on the synthesis of 5-aryl-1,3,4-oxadiazole-2(3H)-one Mannich bases [33,34], we report herein the synthesis of some novel 3,5-disubstituted-1,3,4-oxadiazole derivatives which have been found to posses promising antiinflammatory activity with significantly reduced ulcerogenic effect.…”

mentioning

confidence: 88%

Some Novel Mannich Bases of 5‐(3,4‐Dichlorophenyl)‐1,3,4‐oxadiazole‐2(3H)‐one and Their Anti‐Inflammatory Activity

Koksal

Ozkan-Dagliyan

Ozyazici

et al. 2017

Archiv der Pharmazie

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Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for the treatment of rheumatic arthritis, pain, and many different types of inflammatory disorders, cause serious gastrointestinal (GI) side effects. The free carboxylic acid group existing on their chemical structure is correlated with GI toxicity related with all routine NSAIDs. Replacing this functional group with the 1,3,4-oxadiazole bioisostere is a generally used strategy to obtain an anti-inflammatory agent devoid of GI side effects. In the present work, a novel group of 5-(3,4-dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one Mannich bases were synthesized and characterized on the basis of IR, H NMR, and elemental analysis results. The target compounds were first tested for cytotoxicity to determine a non-toxic concentration for anti-inflammatory screening. Anti-inflammatory effects of the compounds were evaluated by in vitro lipopolysaccharide (LPS)-induced NO production and in vivo carrageenan footpad edema with ulcerogenic profile. In LPS-induced RAW 264.7 macrophages, most of the compounds showed inhibitory activity on nitrite production while compounds 5a, 5h, and 5j exhibited the best profiles by suppressing the NO production. To evaluate the in vivo anti-inflammatory potency of the compounds, the inflammatory response was quantified by increment in paw size in the carrageenan footpad edema assay. The anti-inflammatory data scoring showed that compounds 5a-d, 5g, and 5j, at the dose of 100 mg/kg, exhibited anti-inflammatory activity, which for compound 5g was comparable to that of the reference drug indomethacin with 53.9% and 55.5% inhibition in 60 and 120 min, respectively.

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confidence: 88%

Some Novel Mannich Bases of 5‐(3,4‐Dichlorophenyl)‐1,3,4‐oxadiazole‐2(3H)‐one and Their Anti‐Inflammatory Activity

Koksal

Ozkan-Dagliyan

Ozyazici

et al. 2017

Archiv der Pharmazie

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“…5A) (45). In this assay, IDRs known to promote phase separation enhance the photo-responsive clustering properties of Cry2, causing rapid formation of liquid-like spherical droplets upon blue light-stimulation (46, 47). Fusion of a portion of the MED1 IDR to Cry2-mCherry facilitated the rapid formation of micron-sized spherical droplets upon blue light-stimulation (optoDroplets) (Fig.…”

Section: Med1-idr Participates In Liquid-liquid Phase Separation In Cmentioning

confidence: 99%

Coactivator condensation at super-enhancers links phase separation and gene control

Sabari

Dall’Agnese

Boija

et al. 2018

Science

1,994

111

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Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. Here, we demonstrate that the SE-enriched transcriptional coactivators BRD4 and MED1 form nuclear puncta at SEs that exhibit properties of liquid-like condensates and are disrupted by chemicals that perturb condensates. The intrinsically disordered regions (IDRs) of BRD4 and MED1 can form phase-separated droplets and MED1-IDR droplets can compartmentalize and concentrate transcription apparatus from nuclear extracts. These results support the idea that coactivators form phase-separated condensates at SEs that compartmentalize and concentrate the transcription apparatus, suggest a role for coactivator IDRs in this process, and offer insights into mechanisms involved in control of key cell identity genes.

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“…Because photoexcited CRY2 is known to oligomerize into photobodies (18, 19, 23, 24), it is possible that in darkness nYFP-CRY2 and cCFP-CRY2 interact weakly in a manner sufficient to reconstitute the fluorescent BiFC signal but insufficient to enable oligomerization of CRY2 into photobodies. In response to blue light, nYFP-CRY2 and cCFP-CRY2 may interact with higher affinity to reconstitute not only the fluorescent BiFC signals but also fluorescent photobodies.…”

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confidence: 99%

Photoactivation and inactivation of Arabidopsis cryptochrome 2

Wang

Zuo

Wang

et al. 2016

Science

169

192

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Cryptochromes are blue-light receptors that regulate development and the circadian clock in plants and animals. We found that Arabidopsis cryptochrome 2 (CRY2) undergoes blue light–dependent homodimerization to become physiologically active. We identified BIC1 (blue-light inhibitor of cryptochromes 1) as an inhibitor of plant cryptochromes that binds to CRY2 to suppress the blue light–dependent dimerization, photobody formation, phosphorylation, degradation, and physiological activities of CRY2. We hypothesize that regulated dimerization governs homeostasis of the active cryptochromes in plants and other evolutionary lineages.

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Formation of Arabidopsis Cryptochrome 2 Photobodies in Mammalian Nuclei

Cited by 38 publications

References 31 publications

Some Novel Mannich Bases of 5‐(3,4‐Dichlorophenyl)‐1,3,4‐oxadiazole‐2(3H)‐one and Their Anti‐Inflammatory Activity

Some Novel Mannich Bases of 5‐(3,4‐Dichlorophenyl)‐1,3,4‐oxadiazole‐2(3H)‐one and Their Anti‐Inflammatory Activity

Coactivator condensation at super-enhancers links phase separation and gene control

Photoactivation and inactivation of Arabidopsis cryptochrome 2

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