Phosphorylation of LSD1 by PKCα is crucial for circadian rhythmicity and phase resetting.


:The circadian clock is a self-sustaining oscillator that controls daily rhythms. For the proper circadian gene expression, dynamic changes in chromatin structure are important. Although chromatin modifiers have been shown to play a role in circadian gene expression, the in vivo role of circadian signal-modulated chromatin modifiers at an organism level remains to be elucidated. Here, we provide evidence that the lysine-specific demethylase 1 (LSD1) is phosphorylated by protein kinase Cα (PKCα) in a circadian manner and the phosphorylated LSD1 forms a complex with CLOCK:BMAL1 to facilitate E-box-mediated transcriptional activation. Knockin mice bearing phosphorylation-defective Lsd1(SA/SA) alleles exhibited altered circadian rhythms in locomotor behavior with attenuation of rhythmic expression of core clock genes and impaired phase resetting of circadian clock. These data demonstrate that LSD1 is a key component of the molecular circadian oscillator, which plays a pivotal role in rhythmicity and phase resetting of the circadian clock.


Mol Cell


Molecular cell


Nam HJ,Boo K,Kim D,Han DH,Choe HK,Kim CR,Sun W,Kim H,Kim K,Lee H,Metzger E,Schuele R,Yoo SH,Takahashi JS,Cho S,Son GH,Baek SH




Has Abstract


2014-03-06 00:00:00














  • A yeast intronic splicing enhancer and Nam8p are required for Mer1p-activated splicing.

    abstract::Three introns whose splicing is activated during meiosis in S. cerevisiae contain a Mer1p-dependent splicing enhancer. The enhancer can impose Mer1p-activated splicing upon the constitutively spliced actin intron provided the basal splicing efficiency of actin is first reduced. Of several nonessential splicing factors...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Spingola M,Ares M Jr

    更新日期:2000-08-01 00:00:00

  • Y14 and hUpf3b form an NMD-activating complex.

    abstract::Messenger RNAs with premature translation termination codons (PTCs) are degraded by nonsense-mediated mRNA decay (NMD). In mammals, PTCs are discriminated from physiological stop codons by a process thought to involve the splicing-dependent deposition of an exon junction complex (EJC), EJC-mediated recruitment of Upf3...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Gehring NH,Neu-Yilik G,Schell T,Hentze MW,Kulozik AE

    更新日期:2003-04-01 00:00:00

  • Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p.

    abstract::Posttranslational modification of proliferating cell nuclear antigen (PCNA), an essential processivity clamp for DNA polymerases, by ubiquitin and SUMO contributes to the coordination of DNA replication, damage tolerance, and mutagenesis. Whereas ubiquitination in response to DNA damage promotes the bypass of replicat...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Papouli E,Chen S,Davies AA,Huttner D,Krejci L,Sung P,Ulrich HD

    更新日期:2005-07-01 00:00:00

  • MicroRNA-451 Escapes Global MicroRNA Crisis by Clustered Neighboring MicroRNA-144 During Erythropoiesis.

    abstract::In a recent issue of Molecular Cell, Kretov et al. (2020) demonstrate that microRNA-144 targets Dicer in a negative feedback loop, affecting global canonical microRNA expression in erythrocytes. MicroRNA-451 is refractory to the loss of Dicer because of its Ago2-dependent processing. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Jiang S

    更新日期:2020-06-04 00:00:00

  • CENP-A targeting moves a step back.

    abstract::In a recent issue of Molecular Cell, Pidoux et al. (2009) and Williams et al. (2009) identify S. pombe Scm3 as the proximate factor in the Cnp1/CENP-A deposition pathway, providing a direct connection to centromere-localized Mis16-Mis18. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Baker RE

    更新日期:2009-02-27 00:00:00

  • METTL3 Gains R/W Access to the Epitranscriptome.

    abstract::Epitranscriptomic marks are dynamically placed on mRNA by "writer" or "eraser" enzymes, while "readers" modulate their function accordingly. Lin et al. (2016) now report that the N6-methyladenosine:RNA methyltransferase METTL3 is both a writer and a reader, directly enhancing mRNA translation. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Schumann U,Shafik A,Preiss T

    更新日期:2016-05-05 00:00:00

  • Diabetes mutations delineate an atypical POU domain in HNF-1alpha.

    abstract::Mutations in Hnf-1alpha are the most common Mendelian cause of diabetes mellitus. To elucidate the molecular function of a mutational hotspot, we cocrystallized human HNF-1alpha 83-279 with a high-affinity promoter and solved the structure of the complex. Two identical protein molecules are bound to the promoter. Each...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Chi YI,Frantz JD,Oh BC,Hansen L,Dhe-Paganon S,Shoelson SE

    更新日期:2002-11-01 00:00:00

  • Changing of the guard: how ATM hands off DNA double-strand break signaling to ATR.

    abstract::In a recent issue of Molecular Cell, Shiotani and Zou (2009) elucidate the biochemical mechanism underlying sequential ATM and ATR activation at DNA double-strand breaks, demonstrating that resection transforms ATM substrates into ATR substrates. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Rhind N

    更新日期:2009-03-27 00:00:00

  • Obstacles to Scanning by RNase E Govern Bacterial mRNA Lifetimes by Hindering Access to Distal Cleavage Sites.

    abstract::The diversity of mRNA lifetimes in bacterial cells is difficult to reconcile with the relaxed cleavage site specificity of RNase E, the endonuclease most important for governing mRNA degradation. This enzyme has generally been thought to locate cleavage sites by searching freely in three dimensions. However, our resul...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Richards J,Belasco JG

    更新日期:2019-04-18 00:00:00

  • Genome-wide methylation profiles reveal quantitative views of human aging rates.

    abstract::The ability to measure human aging from molecular profiles has practical implications in many fields, including disease prevention and treatment, forensics, and extension of life. Although chronological age has been linked to changes in DNA methylation, the methylome has not yet been used to measure and compare human ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Hannum G,Guinney J,Zhao L,Zhang L,Hughes G,Sadda S,Klotzle B,Bibikova M,Fan JB,Gao Y,Deconde R,Chen M,Rajapakse I,Friend S,Ideker T,Zhang K

    更新日期:2013-01-24 00:00:00

  • PoxA, yjeK, and elongation factor P coordinately modulate virulence and drug resistance in Salmonella enterica.

    abstract::We report an interaction between poxA, encoding a paralog of lysyl tRNA-synthetase, and the closely linked yjeK gene, encoding a putative 2,3-beta-lysine aminomutase, that is critical for virulence and stress resistance in Salmonella enterica. Salmonella poxA and yjeK mutants share extensive phenotypic pleiotropy, inc...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Navarre WW,Zou SB,Roy H,Xie JL,Savchenko A,Singer A,Edvokimova E,Prost LR,Kumar R,Ibba M,Fang FC

    更新日期:2010-07-30 00:00:00

  • Organelle-Specific Initiation of Autophagy.

    abstract::Autophagy constitutes a prominent mechanism through which eukaryotic cells preserve homeostasis in baseline conditions and in response to perturbations of the intracellular or extracellular microenvironment. Autophagic responses can be relatively non-selective or target a specific subcellular compartment. At least in ...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Sica V,Galluzzi L,Bravo-San Pedro JM,Izzo V,Maiuri MC,Kroemer G

    更新日期:2015-08-20 00:00:00

  • Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37.

    abstract::Activation of protein kinase clients by the Hsp90 system is mediated by the cochaperone protein Cdc37. Cdc37 requires phosphorylation at Ser13, but little is known about the regulation of this essential posttranslational modification. We show that Ser13 of uncomplexed Cdc37 is phosphorylated in vivo, as well as in bin...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Vaughan CK,Mollapour M,Smith JR,Truman A,Hu B,Good VM,Panaretou B,Neckers L,Clarke PA,Workman P,Piper PW,Prodromou C,Pearl LH

    更新日期:2008-09-26 00:00:00

  • Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation.

    abstract::Ubiquitin-mediated proteolysis regulates the activity of diverse receptor systems. Here, we identify Smurf2, a C2-WW-HECT domain ubiquitin ligase and show that Smurf2 associates constitutively with Smad7. Smurf2 is nuclear, but binding to Smad7 induces export and recruitment to the activated TGF beta receptor, where i...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Kavsak P,Rasmussen RK,Causing CG,Bonni S,Zhu H,Thomsen GH,Wrana JL

    更新日期:2000-12-01 00:00:00

  • TOR-tured yeast find a new way to stand the heat.

    abstract::In this issue, Takahara and Maeda (2012) discover that together, Pbp1 and sequestration of the TORC1 complex in cytoplasmic mRNP stress granules provides a negative regulatory mechanism for TORC1 signaling during stress. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Buchan JR,Capaldi AP,Parker R

    更新日期:2012-07-27 00:00:00

  • Activation and inhibition of the receptor histidine kinase AgrC occurs through opposite helical transduction motions.

    abstract::Staphylococcus aureus virulence is regulated when secreted autoinducing peptides (AIPs) are recognized by a membrane-bound receptor histidine kinase (RHK), AgrC. Some AIPs are agonists of virulence gene expression, while others are antagonists. It is unclear how AIP binding regulates AgrC activity. Here, we reconstitu...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Wang B,Zhao A,Novick RP,Muir TW

    更新日期:2014-03-20 00:00:00

  • A negative feedback loop of transcription factors specifies alternative dendritic cell chromatin States.

    abstract::During hematopoiesis, cells originating from the same stem cell reservoir differentiate into distinct cell types. The mechanisms enabling common progenitors to differentiate into alternative cell fates are not fully understood. Here, we identify cell-fate-determining transcription factors (TFs) governing dendritic cel...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Bornstein C,Winter D,Barnett-Itzhaki Z,David E,Kadri S,Garber M,Amit I

    更新日期:2014-12-18 00:00:00

  • Different aa-tRNAs are selected uniformly on the ribosome.

    abstract::Ten E. coli aminoacyl-tRNAs (aa-tRNAs) were assessed for their ability to decode cognate codons on E. coli ribosomes by using three assays that evaluate the key steps in the decoding pathway. Despite a wide variety of structural features, each aa-tRNA exhibited similar kinetic and thermodynamic properties in each assa...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Ledoux S,Uhlenbeck OC

    更新日期:2008-07-11 00:00:00

  • UneCLIPsing HuR nuclear function.

    abstract::The RNA-binding protein HuR, while known to stabilize cytoplasmic mRNAs, is largely nuclear. In this issue of Molecular Cell, Mukherjee et al. (2011) and Lebedeva et al. (2011) identify transcriptome-wide HuR-RNA interactions using PAR-CLIP, unveiling HuR's nuclear role in pre-mRNA processing. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Srikantan S,Gorospe M

    更新日期:2011-08-05 00:00:00

  • General and versatile autoinhibition of PLC isozymes.

    abstract::Phospholipase C (PLC) isozymes are directly activated by heterotrimeric G proteins and Ras-like GTPases to hydrolyze phosphatidylinositol 4,5-bisphosphate into the second messengers diacylglycerol and inositol 1,4,5-trisphosphate. Although PLCs play central roles in myriad signaling cascades, the molecular details of ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Hicks SN,Jezyk MR,Gershburg S,Seifert JP,Harden TK,Sondek J

    更新日期:2008-08-08 00:00:00

  • Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation.

    abstract::DNA methylation is an essential epigenetic mark in mammals that has to be re-established after each round of DNA replication. The protein UHRF1 is essential for this process; it has been proposed that the protein targets newly replicated DNA by cooperatively binding hemi-methylated DNA and H3K9me2/3, but this model le...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Ferry L,Fournier A,Tsusaka T,Adelmant G,Shimazu T,Matano S,Kirsh O,Amouroux R,Dohmae N,Suzuki T,Filion GJ,Deng W,de Dieuleveult M,Fritsch L,Kudithipudi S,Jeltsch A,Leonhardt H,Hajkova P,Marto JA,Arita K,Shinkai Y

    更新日期:2017-08-17 00:00:00

  • Nuclear RNA Decay Pathways Aid Rapid Remodeling of Gene Expression in Yeast.

    abstract::In budding yeast, the nuclear RNA surveillance system is active on all pre-mRNA transcripts and modulated by nutrient availability. To test the role of nuclear surveillance in reprogramming gene expression, we identified transcriptome-wide binding sites for RNA polymerase II and the exosome cofactors Mtr4 (TRAMP compl...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Bresson S,Tuck A,Staneva D,Tollervey D

    更新日期:2017-03-02 00:00:00

  • Psh1 is an E3 ubiquitin ligase that targets the centromeric histone variant Cse4.

    abstract::Cse4 is a variant of histone H3 that is incorporated into a single nucleosome at each centromere in budding yeast. We have discovered an E3 ubiquitin ligase, called Psh1, which controls the cellular level of Cse4 via ubiquitylation and proteolysis. The activity of Psh1 is dependent on both its RING and zinc finger dom...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Hewawasam G,Shivaraju M,Mattingly M,Venkatesh S,Martin-Brown S,Florens L,Workman JL,Gerton JL

    更新日期:2010-11-12 00:00:00

  • Licensing of Centromeric Chromatin Assembly through the Mis18α-Mis18β Heterotetramer.

    abstract::Centromeres are specialized chromatin domains specified by the centromere-specific CENP-A nucleosome. The stable inheritance of vertebrate centromeres is an epigenetic process requiring deposition of new CENP-A nucleosomes by HJURP. We show HJURP is recruited to centromeres through a direct interaction between the HJU...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Nardi IK,Zasadzińska E,Stellfox ME,Knippler CM,Foltz DR

    更新日期:2016-03-03 00:00:00

  • An Arginine Nexus in the RNA Polymerase II CTD.

    abstract::In this issue of Molecular Cell,Sharma et al. (2019) show that normal cell growth requires conversion of an arginine residue in the RNA polymerase II C-terminal domain (CTD) to citrulline, uncovering a potential regulatory pathway involving opposing arginine modifications. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Corden JL

    更新日期:2019-01-03 00:00:00

  • Structural Basis for Guide RNA Processing and Seed-Dependent DNA Targeting by CRISPR-Cas12a.

    abstract::The CRISPR-associated protein Cas12a (Cpf1), which has been repurposed for genome editing, possesses two distinct nuclease activities: endoribonuclease activity for processing its own guide RNAs and RNA-guided DNase activity for target DNA cleavage. To elucidate the molecular basis of both activities, we determined cr...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Swarts DC,van der Oost J,Jinek M

    更新日期:2017-04-20 00:00:00

  • A soluble form of the pilus protein FimA targets the VDAC-hexokinase complex at mitochondria to suppress host cell apoptosis.

    abstract::Inhibition of apoptotic response of host cells during an early phase of infection is a strategy used by many enteroinvasive bacterial pathogens to enhance their survival. Here, we report the identification of a soluble form of the pilus protein FimA from the culture supernatants of E. coli K1, Salmonella, and Shigella...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Sukumaran SK,Fu NY,Tin CB,Wan KF,Lee SS,Yu VC

    更新日期:2010-03-26 00:00:00

  • The yeast G protein alpha subunit Gpa1 transmits a signal through an RNA binding effector protein Scp160.

    abstract::In yeast Saccharomyces cerevisiae the G protein betagamma subunits (Ste4/Ste18) have long been known to transmit the signal required for mating. Here we demonstrate that GTPase-deficient mutants of Galpha (Gpa1) directly activate the mating response pathway. We also show that signaling by activated Gpa1 requires direc...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Guo M,Aston C,Burchett SA,Dyke C,Fields S,Rajarao SJ,Uetz P,Wang Y,Young K,Dohlman HG

    更新日期:2003-08-01 00:00:00

  • The special delivery of a tail-anchored protein: why it pays to use a dedicated courier.

    abstract::The membrane-spanning C-terminal regions in tail-anchored proteins must be recognized and delivered posttranslationally to the endoplasmic reticulum or mitochondrial membrane. A paper in this issue of Molecular Cell (Wang et al., 2010) and another recent report (Mariappan et al., 2010) delineate early steps in this pa...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Brodsky JL

    更新日期:2010-10-08 00:00:00

  • A Therapeutic Double Whammy: Transcriptional or Post-transcriptional Suppression of Microsatellite Repeat Toxicity by Cas9.

    abstract::Microsatellite expansion diseases are caused by unstable tandem repeats of 3-10 nucleotides that become pathogenic beyond a threshold number of copies. Two groups present different approaches to reduce pathogenesis by targeting deactivated Cas9 to either the DNA (Pinto et al., 2017) or the RNA (Batra et al., 2017) rep...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Rao AN,Cooper TA

    更新日期:2017-11-02 00:00:00