Genomes and Genes
Gene Symbol: Cry2
Description: cryptochrome 2 (photolyase-like)
Alias: AV006279, D130054K12Rik, cryptochrome-2
- Czarna A, Breitkreuz H, Mahrenholz C, Arens J, Strauss H, Wolf E. Quantitative analyses of cryptochrome-mBMAL1 interactions: mechanistic insights into the transcriptional regulation of the mammalian circadian clock. J Biol Chem. 2011;286:22414-25 pubmed publisher..Moreover, our study suggests the design of peptidic inhibitors targeting the interaction of the mCRY1 tail with mBMAL1. ..
- Iijima M, Yamaguchi S, van der Horst G, Bonnefont X, Okamura H, Shibata S. Altered food-anticipatory activity rhythm in Cryptochrome-deficient mice. Neurosci Res. 2005;52:166-73 pubmed..However, it is also important to note that mCry deficiency affects the stability and development of RF-induced anticipatory locomotor activity. ..
- Xu Y, Toh K, Jones C, Shin J, Fu Y, Ptacek L. Modeling of a human circadian mutation yields insights into clock regulation by PER2. Cell. 2007;128:59-70 pubmed..Altering CKIdelta dosage modulates the S662 phenotype demonstrating that CKIdelta can regulate period through PER2 in vivo. Modeling a naturally occurring human variant in mice has yielded novel insights into PER2 regulation. ..
- Stratmann M, Stadler F, Tamanini F, van der Horst G, Ripperger J. Flexible phase adjustment of circadian albumin D site-binding protein (DBP) gene expression by CRYPTOCHROME1. Genes Dev. 2010;24:1317-28 pubmed publisher..Our data indicate that fine-tuning of circadian transcription in the liver is even more sophisticated than expected. ..
- Thompson C, Selby C, Partch C, Plante D, Thresher R, Araujo F, et al. Further evidence for the role of cryptochromes in retinohypothalamic photoreception/phototransduction. Brain Res Mol Brain Res. 2004;122:158-66 pubmed
- Sujino M, Masumoto K, Yamaguchi S, van der Horst G, Okamura H, Inouye S. Suprachiasmatic nucleus grafts restore circadian behavioral rhythms of genetically arrhythmic mice. Curr Biol. 2003;13:664-8 pubmed
- Ukai Tadenuma M, Yamada R, Xu H, Ripperger J, Liu A, Ueda H. Delay in feedback repression by cryptochrome 1 is required for circadian clock function. Cell. 2011;144:268-81 pubmed publisher..A genetic complementation assay in Cry1(-/-):Cry2(-/-) cells revealed that substantial delay of Cry1 expression is required to restore circadian rhythmicity, and its ..
- Wisor J, O Hara B, Terao A, Selby C, Kilduff T, Sancar A, et al. A role for cryptochromes in sleep regulation. BMC Neurosci. 2002;3:20 pubmedThe cryptochrome 1 and 2 genes (cry1 and cry2) are necessary for the generation of circadian rhythms, as mice lacking both of these genes (cry1,2-/-) lack circadian rhythms...
- Bur I, Cohen Solal A, Carmignac D, Abecassis P, Chauvet N, Martin A, et al. The circadian clock components CRY1 and CRY2 are necessary to sustain sex dimorphism in mouse liver metabolism. J Biol Chem. 2009;284:9066-73 pubmed publisher..Here we show that dimorphic liver metabolism is altered when the circadian regulators Cryptochromes, Cry1 and Cry2, are inactivated...
- Duong H, Robles M, Knutti D, Weitz C. A molecular mechanism for circadian clock negative feedback. Science. 2011;332:1436-9 pubmed publisher..These findings provide a function for the PER complex and a molecular mechanism for circadian clock negative feedback. ..
- Yamaguchi S, Isejima H, Matsuo T, Okura R, Yagita K, Kobayashi M, et al. Synchronization of cellular clocks in the suprachiasmatic nucleus. Science. 2003;302:1408-12 pubmed..Na+-dependent action potentials contributed to establishing cellular synchrony and maintaining spontaneous oscillation across the SCN. ..
- Xing W, Busino L, Hinds T, Marionni S, Saifee N, Bush M, et al. SCF(FBXL3) ubiquitin ligase targets cryptochromes at their cofactor pocket. Nature. 2013;496:64-8 pubmed publisher..Here we report crystal structures of mammalian CRY2 in its apo, FAD-bound and FBXL3-SKP1-complexed forms...
- Miyamoto Y, Sancar A. Circadian regulation of cryptochrome genes in the mouse. Brain Res Mol Brain Res. 1999;71:238-43 pubmed..In humans and mice, two cryptochromes, called CRY1 and CRY2, have been identified...
- Vitaterna M, Selby C, Todo T, Niwa H, Thompson C, Fruechte E, et al. Differential regulation of mammalian period genes and circadian rhythmicity by cryptochromes 1 and 2. Proc Natl Acad Sci U S A. 1999;96:12114-9 pubmed..Humans and mice have two cryptochrome (Cry) genes. A previous study showed that mice lacking the Cry2 gene had reduced sensitivity to acute light induction of the circadian gene mPer1 in the suprachiasmatic nucleus (..
- Fu L, Patel M, Bradley A, Wagner E, Karsenty G. The molecular clock mediates leptin-regulated bone formation. Cell. 2005;122:803-15 pubmed..Thus, leptin determines the extent of bone formation by modulating, via sympathetic signaling, osteoblast proliferation through two antagonistic pathways, one of which involves the molecular clock. ..
- Kobayashi K, Kanno S, Smit B, van der Horst G, Takao M, Yasui A. Characterization of photolyase/blue-light receptor homologs in mouse and human cells. Nucleic Acids Res. 1998;26:5086-92 pubmed..Using green fluorescent protein fused peptides we showed that the C-terminal region of the mouse CRY2 protein contains a unique nuclear localization signal, which is absent in the CRY1 protein...
- Ramsey K, Yoshino J, Brace C, Abrassart D, Kobayashi Y, Marcheva B, et al. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science. 2009;324:651-4 pubmed publisher..In turn, the circadian transcription factor CLOCK binds to and up-regulates Nampt, thus completing a feedback loop involving NAMPT/NAD+ and SIRT1/CLOCK:BMAL1. ..
- Busino L, Bassermann F, Maiolica A, Lee C, Nolan P, Godinho S, et al. SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins. Science. 2007;316:900-4 pubmed..Among its downstream targets, two genes, Cry1 and Cry2, encode inhibitors of the Clock-Bmal1 complex that establish a negative-feedback loop...
- Ozturk N, Lee J, Gaddameedhi S, Sancar A. Loss of cryptochrome reduces cancer risk in p53 mutant mice. Proc Natl Acad Sci U S A. 2009;106:2841-6 pubmed publisher..These results suggest alternative therapeutic approaches in management of cancers associated with a p53 mutation. ..
- Cretenet G, Le Clech M, Gachon F. Circadian clock-coordinated 12 Hr period rhythmic activation of the IRE1alpha pathway controls lipid metabolism in mouse liver. Cell Metab. 2010;11:47-57 pubmed publisher..The resulting aberrant circadian lipid metabolism in mice devoid of the circadian clock could be involved in the appearance of the associated metabolic syndrome. ..
- Mendoza J, Albrecht U, Challet E. Behavioural food anticipation in clock genes deficient mice: confirming old phenotypes, describing new phenotypes. Genes Brain Behav. 2010;9:467-77 pubmed publisher..Interestingly, rescued behavioural rhythms in Per2(Brdm1);Cry2(-/-) mice in DD were totally entrained to feeding time and re-synchronized after phase-shifts of mealtime, ..
- Mrosovsky N. Further characterization of the phenotype of mCry1/mCry2-deficient mice. Chronobiol Int. 2001;18:613-25 pubmed..One possible explanation of such predark activity is that some damped endogenous process is spared in mCry1/mCry2 double-knockout mice. ..
- Kume K, Zylka M, Sriram S, Shearman L, Weaver D, Jin X, et al. mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell. 1999;98:193-205 pubmed..Luciferase reporter gene assays show that mCRY1 or mCRY2 alone abrogates CLOCK:BMAL1-E box-mediated transcription. The mPER and mCRY proteins appear to inhibit the transcriptional complex differentially. ..
- Thresher R, Vitaterna M, Miyamoto Y, Kazantsev A, Hsu D, Petit C, et al. Role of mouse cryptochrome blue-light photoreceptor in circadian photoresponses. Science. 1998;282:1490-4 pubmed..Mice lacking the cryptochrome 2 blue-light photoreceptor gene (mCry2) were tested for circadian clock-related functions...
- Asher G, Reinke H, Altmeyer M, Gutierrez Arcelus M, Hottiger M, Schibler U. Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding. Cell. 2010;142:943-53 pubmed publisher..Our results show that Parp-1 knockout mice exhibit impaired food entrainment of peripheral circadian clocks and support a role for PARP-1 in connecting feeding with the mammalian timing system. ..
- Ozber N, Baris I, Tatlici G, Gur I, Kilinc S, Unal E, et al. Identification of two amino acids in the C-terminal domain of mouse CRY2 essential for PER2 interaction. BMC Mol Biol. 2010;11:69 pubmed publisher..Our results identify mCRY2 amino acid residues that interact with the mPER2 binding region and suggest the potential for rational drug design to inhibit CRYs for specific therapeutic approaches. ..
- Lamia K, Papp S, Yu R, Barish G, Uhlenhaut N, Jonker J, et al. Cryptochromes mediate rhythmic repression of the glucocorticoid receptor. Nature. 2011;480:552-6 pubmed publisher..These results reveal a specific mechanism through which cryptochromes couple the activity of clock and receptor target genes to complex genomic circuits underpinning normal metabolic homeostasis. ..
- Zhao W, Malinin N, Yang F, Staknis D, Gekakis N, Maier B, et al. CIPC is a mammalian circadian clock protein without invertebrate homologues. Nat Cell Biol. 2007;9:268-75 pubmed..Our results suggest that negative feedback in the mammalian circadian clock is divided into distinct pathways, and that the addition of new genes has contributed to the complexity of vertebrate clocks. ..
- Kang T, Reardon J, Kemp M, Sancar A. Circadian oscillation of nucleotide excision repair in mammalian brain. Proc Natl Acad Sci U S A. 2009;106:2864-7 pubmed publisher..The circadian oscillation of the repair capacity is caused at least in part by the circadian oscillation of the xeroderma pigmentosum A DNA damage recognition protein. ..
- Cheng M, Bullock C, Li C, Lee A, Bermak J, Belluzzi J, et al. Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature. 2002;417:405-10 pubmed..The high expression of PKR2 mRNA within the SCN and the positive feedback of PK2 on its own transcription through activation of PKR2 suggest that PK2 may also function locally within the SCN to synchronize output. ..
- Van Gelder R, Wee R, Lee J, Tu D. Reduced pupillary light responses in mice lacking cryptochromes. Science. 2003;299:222 pubmed
- Lee C, Weaver D, Reppert S. Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock. Mol Cell Biol. 2004;24:584-94 pubmed..We thus propose that the CKIepsilon-binding domain is critical not only for mPER phosphorylation but also for a functioning circadian clock. ..
- Koike N, Yoo S, Huang H, Kumar V, Lee C, Kim T, et al. Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science. 2012;338:349-54 pubmed publisher..We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling. ..
- Yagita K, Yamaguchi S, Tamanini F, van der Horst G, Hoeijmakers J, Yasui A, et al. Dimerization and nuclear entry of mPER proteins in mammalian cells. Genes Dev. 2000;14:1353-63 pubmed..Deletion analysis suggests that the interplay of the CLD and NLS proposed to regulate nuclear entry of PER in Drosophila is conserved in mammals, but with the novel twist that mPER3 can act as the dimerizing partner. ..
- Maywood E, Chesham J, O Brien J, Hastings M. A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits. Proc Natl Acad Sci U S A. 2011;108:14306-11 pubmed publisher..Thus, a hierarchy of paracrine neuropeptidergic signals determines cell- and circuit-level circadian pacemaking in the SCN. ..
- Doi M, Ishida A, Miyake A, Sato M, Komatsu R, Yamazaki F, et al. Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus. Nat Commun. 2011;2:327 pubmed publisher..Thus, RGS16-dependent temporal regulation of intracellular G protein signalling coordinates the intercellular synchrony of SCN pacemaker neurons and thereby defines the 24 h rhythm in behaviour. ..
- Oster H, Yasui A, van der Horst G, Albrecht U. Disruption of mCry2 restores circadian rhythmicity in mPer2 mutant mice. Genes Dev. 2002;16:2633-8 pubmed..mCry2 can act as a nonallelic suppressor of mPer2, which points to direct or indirect interactions of PER2 and CRY2 proteins...
- Oishi K, Miyazaki K, Kadota K, Kikuno R, Nagase T, Atsumi G, et al. Genome-wide expression analysis of mouse liver reveals CLOCK-regulated circadian output genes. J Biol Chem. 2003;278:41519-27 pubmed..We also compared expression profiles with those of Cryptochromes (Cry1 and Cry2) double knockout mice...
- Lee S, Donehower L, Herron A, Moore D, Fu L. Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice. PLoS ONE. 2010;5:e10995 pubmed publisher..However, it remains unclear how circadian rhythm in cell proliferation is generated in vivo and why disruption of circadian rhythm may lead to tumorigenesis...
- Shearman L, Sriram S, Weaver D, Maywood E, Chaves I, Zheng B, et al. Interacting molecular loops in the mammalian circadian clock. Science. 2000;288:1013-9 pubmed..PERIOD2 is a positive regulator of the Bmal1 loop, and CRYPTOCHROMES are the negative regulators of the Period and Cryptochrome cycles. ..
- Ono D, Honma S, Honma K. Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus. Nat Commun. 2013;4:1666 pubmed publisherCryptochrome (Cry) 1 and Cry2 are regarded as critical components for circadian rhythm generation in mammals...
- Doi M, Takahashi Y, Komatsu R, Yamazaki F, Yamada H, Haraguchi S, et al. Salt-sensitive hypertension in circadian clock-deficient Cry-null mice involves dysregulated adrenal Hsd3b6. Nat Med. 2010;16:67-74 pubmed publisher..We show that mice lacking the core clock components Cryptochrome-1 (Cry1) and Cryptochrome-2 (Cry2) (Cry-null mice) show salt-sensitive hypertension due to abnormally high synthesis of the mineralocorticoid ..
- Kojima S, Matsumoto K, Hirose M, Shimada M, Nagano M, Shigeyoshi Y, et al. LARK activates posttranscriptional expression of an essential mammalian clock protein, PERIOD1. Proc Natl Acad Sci U S A. 2007;104:1859-64 pubmed..These data indicate that mLARKs are novel posttranscriptional regulators of mammalian circadian clocks. ..
- Sanada K, Harada Y, Sakai M, Todo T, Fukada Y. Serine phosphorylation of mCRY1 and mCRY2 by mitogen-activated protein kinase. Genes Cells. 2004;9:697-708 pubmed..These results illustrate a model of MAPK-mediated negative regulation of mCRY function by phosphorylation at the specific Ser residue. ..
- Kurabayashi N, Hirota T, Sakai M, Sanada K, Fukada Y. DYRK1A and glycogen synthase kinase 3beta, a dual-kinase mechanism directing proteasomal degradation of CRY2 for circadian timekeeping. Mol Cell Biol. 2010;30:1757-68 pubmed publisher..Although CRY2 undergoes rhythmic phosphorylation in its C-terminal tail, structurally distinct from the CRY1 tail, little is ..
- Matsuo T, Yamaguchi S, Mitsui S, Emi A, Shimoda F, Okamura H. Control mechanism of the circadian clock for timing of cell division in vivo. Science. 2003;302:255-9 pubmed..In contrast, the circadian clockwork oscillated independently of the cell cycle in single cells. Thus, the intracellular circadian clockwork can control the cell-division cycle directly and unidirectionally in proliferating cells. ..
- Miyamoto Y, Sancar A. Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract as the photoactive pigments for setting the circadian clock in mammals. Proc Natl Acad Sci U S A. 1998;95:6097-102 pubmed..We have found that the two blue-light photoreceptors, cryptochromes 1 and 2 (CRY1 and CRY2), recently discovered in mammals are specifically expressed in the ganglion cell and inner nuclear layers of the ..
- Yoshitane H, Takao T, Satomi Y, Du N, Okano T, Fukada Y. Roles of CLOCK phosphorylation in suppression of E-box-dependent transcription. Mol Cell Biol. 2009;29:3675-86 pubmed publisher..Coexpression of CRY2 in NIH 3T3 cells inhibited the phosphorylation of CLOCK, whereas CIPC coexpression markedly stimulated ..
- Siepka S, Yoo S, Park J, Song W, Kumar V, Hu Y, et al. Circadian mutant Overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression. Cell. 2007;129:1011-23 pubmed..In Ovtm mice, expression of the PERIOD proteins PER1 and PER2 is reduced; however, the CRY proteins CRY1 and CRY2 are unchanged...
- Richards J, All S, Skopis G, Cheng K, Compton B, Srialluri N, et al. Opposing actions of Per1 and Cry2 in the regulation of Per1 target gene expression in the liver and kidney. Am J Physiol Regul Integr Comp Physiol. 2013;305:R735-47 pubmed publisher..Recent work has highlighted the potential role of Per1 in repression of Cry2. Therefore, we postulated that Per1 potentially activates target genes through a Cry2-Clock/Bmal1-dependent ..
- Papp S, Huber A, Jordan S, Kriebs A, Nguyen M, Moresco J, et al. DNA damage shifts circadian clock time via Hausp-dependent Cry1 stabilization. elife. 2015;4: pubmed publisherThe circadian transcriptional repressors cryptochrome 1 (Cry1) and 2 (Cry2) evolved from photolyases, bacterial light-activated DNA repair enzymes...
- Kondratov R, Shamanna R, Kondratova A, Gorbacheva V, Antoch M. Dual role of the CLOCK/BMAL1 circadian complex in transcriptional regulation. FASEB J. 2006;20:530-2 pubmed
- Sakakida Y, Miyamoto Y, Nagoshi E, Akashi M, Nakamura T, Mamine T, et al. Importin alpha/beta mediates nuclear transport of a mammalian circadian clock component, mCRY2, together with mPER2, through a bipartite nuclear localization signal. J Biol Chem. 2005;280:13272-8 pubmed..These results suggest that the importin alpha/beta system is involved in nuclear entry of mammalian clock components, which is indispensable to transcriptional oscillation of clock genes. ..
- Tanida M, Yamatodani A, Niijima A, Shen J, Todo T, Nagai K. Autonomic and cardiovascular responses to scent stimulation are altered in cry KO mice. Neurosci Lett. 2007;413:177-82 pubmed..GVNA increase were not observed in Cryptochrome (Cry)-deficient mice, which harbor mutations in both cry1 and cry2 and lack normal circadian rhythms...
- Miyazaki K, Wakabayashi M, Chikahisa S, Sei H, Ishida N. PER2 controls circadian periods through nuclear localization in the suprachiasmatic nucleus. Genes Cells. 2007;12:1225-34 pubmed..The nuclear entry of endogenous PER2, CRY1 and CRY2 was delayed in the suprachiasmatic nucleus (SCN) of NLD(-) PER2 TG mice under constant darkness, whereas that of ..