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CRYs' C termini are essential for nuclear localization but not necessary for the suppression of CLOCK/BMAL1 activation
we investigated the structure/function relationships of Xenopus laevis CRY1 (xCRY1) and xCRY2 in cultured cells
Cry1 is expressed in the olfactory bulb of newborn and juvenile rabbits.
this study identified two distinct light chain 3 (LC3)-interacting region (LIR) motifs on CRY1 that exert circadian glycemic control by regulating CRY1 degradation, revealing LIRs as potential targets for controlling hyperglycemia.
In colorectal cancer, higher expression of cry1 in the right-sided colon tumor tissue was associated with worse survival in women and the expression of cry1 in the left-sided colorectum was significantly higher in the adjacent tissue compared to tumor in men but not in women
Neuroglobin correlates with cryptochrome-1 in obstructive sleep apnea with primary aldosteronism
CRY-1 was expressed in 94% of the CLL patients at diagnosis. The median CRY-1 relative gene expression level (0.006) stratified patients into high and low expression groups. Forty of 100 (40%) CLL patients showed high CRY-1, 54/100 (54%) showed low CRY-1, and 6/100 (6%) had undetectable CRY-1 gene expression.
Independent silencing of CRY1 and CRY2 genes in HAC15 cells resulted in a mild upregulation of HSD3B2 without affecting HSD3B1 expression. In conclusion, our results support the hypothesis that CRY1 and CRY2, being AngII-regulated genes, and showing a differential expression in APAs when compared with the adjacent adrenal cortex, might be involved in adrenal cell function, and in the regulation of aldosterone production
The studies in this review reported contrasting results about the association of different single nucleotide polymorphisms (SNPs) in clock genes and Major Depressive Disorder. The most consistent result reported the association between SNP rs2287161 of CRY1 and MDD development.
CRY1/2 serve as corepressors for many NRs.
Study confirms the prognostic role of CRY1 in chronic lymphocytic leukemia, as its aberrant methylation and expression is associated with high risk of treatment initiation and survival.
CRY1 SNP rs714359 showed nominally significant association with the problematicity of seasonal variations (problematic vs. no variation) of mood disorder. The set-based analysis did not support these associations. However, the CRY1 haplotype TAG including rs714359 showed nominally significant association with the problematicity of seasonal variations in mood disorder.
CRY1 variants were not associated with major depressive disorder.
Our findings suggest that CLOCK and CRY1 polymorphisms might be involved in individual susceptibility to abdominal obesity in Chinese Han population.
Knockout-rescue embryonic stem cell-derived mouse reveals that CRY1 determines circadian period through both its degradation-dependent and -independent pathways.
The present study identified USP7 and TDP-43 as the regulators of CRY1 and CRY2, underscoring the significance of the stability control process of CRY proteins for period determination in the mammalian circadian clockwork.
Altered CRY1 and CRY2 expression patterns and the interplay with the genetic landscape in colon cancer cells may underlie phenotypic divergence.
possible circadian rhythm in full-term placental expression
Given the distinct characteristics of the C-terminal tails of the CRY1 and CRY2 proteins, our study addresses a long-standing hypothesis that the ratio of these two CRY molecules affects the clock period.
Overexpression of CRY1 protects against the development of atherosclerosis via the TLR/NFkappaB pathway
Collectively, these data show that KPNB1 is required for timely nuclear import of PER/CRY in the negative feedback regulation of the circadian clock.
these observations suggest a biologically plausible season-dependent association between SNPs at CRY1, CRY2 and MTNR1B and glucose homeostasis.
CRY1 and CRY2 variants showed nominal association with the metabolic syndrome components, hypertension and triglyceride levels.
These results provide the first evidence of a correlation between dysregulation of Cry1 and male reproductive defects in mice, indicating that Cry1 plays a critical role in maintaining normal testicular function.
CRY1 regulates adipogenic differentiation through modulating the canonical Wnt/beta-catenin signaling pathway.
insulin-activated SREBP1c downregulates gluconeogenesis through CRY1-mediated FOXO1 degradation.
Circadian clock cryptochrome proteins Cry1 and Cry2 regulate autoimmunity.
Deleting the Cry1 intronic enhancer in mice shortens the circadian locomotor period
Data show that CRY1 binds directly to the PAS domain core of CLOCK:BMAL1, driven primarily by interaction with the CLOCK PAS-B domain.
CRY1/2 seem to repress a distinct subset of PPAR delta target genes in muscle compared to the co-repressor NCOR1. In vivo, genetic disruption of Cry1 and Cry2 enhances sprint exercise performance in mice.
hnRNP Q binds to mCry1 mRNA via the 5'UTR. Furthermore, hnRNP Q inhibits the translation of mCry1 mRNA, leading to altered rhythmicity in the mCRY1 protein profile.
In vivo knockdown of Rfk, Riboflavin (vitamin B2) kinase essential for FAD synthesis, altered the expression rhythms of CRY1, CRY2, and PER1
Cryptochrome 1 in retinal cone photoreceptors suggests a novel functional role in mammals.
polyamines control the circadian period in cultured cells and animals by regulating the interaction between the core clock repressors PER2 and CRY1
Data show that cryptochrome Cry1 and Cry2 expression must be circadian and appropriately phased to support rhythms, and arginine vasopressin (AVP) receptor signaling is required to impose circuit-level circadian function.
uncovered a novel biological role for CUL4A-DDB1-CDT2 E3 ligase that regulates molecular circadian behaviors via promoting ubiquitination-dependent degradation of CRY1
Data suggest that cryptochromes (Cry1 and Cry2) mediate periodic binding of Ck2b (casein kinase 2beta) to Bmal1 (aryl hydrocarbon receptor nuclear translocator-like protein) and thus inhibit Bmal1-Ser90 phosphorylation by Ck2a (casein kinase 2alpha).
demonstrate that genotoxic stress stimulates Cry1 phosphorylation and its deubiquitination by Herpes virus associated ubiquitin-specific protease (Hausp, a.k.a Usp7), stabilizing Cry1 and shifting circadian clock time
Cry1/Cry2-deficient mice had significantly lower N6- methyladenosine methylation of RNA and lost the circadian rhythm of N6-methyladenosine levels in RNA.
these results suggested that the overexpression of CRY1 inhibited sleep deprivation-induced vascular inflammation that might be associated with NF-kappaB and cAMP/PKA pathways.
results suggest that HBI1 acts as a new CRY1-interacting protein and that the signaling mechanism of CRY1 involves repression of HBI1 transcriptional activity by direct CRY1-HBI1 interaction
AGB1 inhibition of photomorphogenesis is mediated, through the repression of the DNA-binding activity of HY5 by the physical AGB1-HY5 interaction, and the mechanism of CRY1 control of photomorphogenesis involves positive regulation of the DNA-binding activity of HY5 by the CRY1--AGB1 interaction, which prevents the association of AGB1 with HY5
FIN219 and CRY1 negatively regulated each other by direct interaction in response to jasmonate under blue light.
The results demonstrate a CRY-BIC negative-feedback circuitry that regulates the activity of each other.
Exposure to blue light is required for an in vivo-association of CRY1 and CRY2 with COP1.
Data suggest that cry1 mutation L407F exhibits hyperactivity which is not related to a higher FADH occupancy of the photoreceptor but is caused by a structural alteration close to the ATP-binding site.
Nitrogen signaling functions as a modulator of nuclear CRY1 protein abundance, as well as the input signal for the central circadian clock to interfere with the normal flowering process.
Data show that the effect of 3-bromo-7-nitroindazole (3B7N) treatment on gene expression in cryptochromes cry1cry2 is considerably smaller than that in the wild type, indicating that 3B7N specifically interrupts cryptochrome function in the control of seedling development in a light-dependent manner.
These data illustrate that in vivo modulation by metabolites in the cellular environment may play an important role in cryptochrome signaling.
For growth under a canopy, where blue light is diminished, CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH transcription factors, PIF4 and PIF5.
CRY1 represses auxin biosynthesis in response to elevated temperature through PIF4.
CRY1 inhibits hypocotyl elongation in blue light through CNT1-mediated repression of the auxin/BR/GAresponsive gene expression.
Reactive oxygen species formation results from cry1 activation and induces cell death in insect cell cultures.
The study shows that ATP binding and aspartate protonation enhance photoinduced electron transfer in plant CRY1.
photoreduction-deficient Trp-triad mutations of CRY1 remained physiologically and biochemically active in Arabidopsis plants.
Based on the loss of degradation of cry2 after prolonged darkness and loss of reversibility of photoactivated cry1 by a pulse of green light, we estimate the in vivo half-lives of the signaling states of cry1 and cry2 to be in the range of 5 and 16 min.
Data indicate that the green light (GL) opposition of red light (RL) responses persists in phyA, phyB, cry1cry2 and phot2 mutants, and the response requires phot1 and NPH3.
Perception of light by phyA, cry1 or phyB activates ROC1; this in turn reduces the intensity of brassinosteroid signalling and fine-tunes seedling de-etiolation.
Both cry1 and gpa1 showed reduced accumulation of anthocyanin under blue light. Both gpa1 and cry1 mutants showed reduced GTP-binding activity. It is propsed that cry1-mediated post-translational modification of GPA1 alters its GTP-binding activity.
in plants, the phyB/CRY1 interaction may mediate cross-talk between the red/far-red- and blue/UV-sensing pathways, enabling fine-tuning of light responses to different spectral inputs
This gene encodes a flavin adenine dinucleotide-binding protein that is a key component of the circadian core oscillator complex, which regulates the circadian clock. The encoded protein is widely conserved across plants and animals. Loss of the related gene in mouse results in a shortened circadian cycle in complete darkness.
cryptochrome 1 (photolyase-like)
, cryptochrome 2 (photolyase-like)
, cryptochrome 1