Genomes and Genes
14 3 3 proteins
Summary: A large family of signal-transducing adaptor proteins present in wide variety of eukaryotes. They are PHOSPHOSERINE and PHOSPHOTHREONINE binding proteins involved in important cellular processes including SIGNAL TRANSDUCTION; CELL CYCLE control; APOPTOSIS; and cellular stress responses. 14-3-3 proteins function by interacting with other signal-transducing proteins and effecting changes in their enzymatic activity and subcellular localization. The name 14-3-3 derives from numerical designations used in the original fractionation patterns of the proteins.
- Yip M, Ramm G, Larance M, Hoehn K, Wagner M, Guilhaus M, et al. CaMKII-mediated phosphorylation of the myosin motor Myo1c is required for insulin-stimulated GLUT4 translocation in adipocytes. Cell Metab. 2008;8:384-98 pubmed publisher..These data suggest that insulin regulates Myo1c function via CaMKII-dependent phosphorylation, and these events play a role in insulin-regulated GLUT4 trafficking in adipocytes likely involving Myo1c motor activity. ..
- Holman G, Sakamoto K. Regulating the motor for GLUT4 vesicle traffic. Cell Metab. 2008;8:344-6 pubmed publisher..Now, Yip et al. (2008) link myosin-1c to insulin signaling by demonstrating direct CaMKII-driven phosphorylation of this critical motor protein. ..
- Wehr M, Reinecke L, Botvinnik A, Rossner M. Analysis of transient phosphorylation-dependent protein-protein interactions in living mammalian cells using split-TEV. BMC Biotechnol. 2008;8:55 pubmed publisher..Given the high sensitivity of the split-TEV system, all assays were performed in multi-plate formats and could be adapted for higher throughput to screen for pharmacologically active substances. ..
- Mohammad D, Yaffe M. 14-3-3 proteins, FHA domains and BRCT domains in the DNA damage response. DNA Repair (Amst). 2009;8:1009-17 pubmed publisher..In addition, we consider the role of 14-3-3 proteins and the Chk2 FHA domain in initiating and maintaining cell cycle arrest. ..
- Schumacher B, Mondry J, Thiel P, Weyand M, Ottmann C. Structure of the p53 C-terminus bound to 14-3-3: implications for stabilization of the p53 tetramer. FEBS Lett. 2010;584:1443-8 pubmed publisher..The structure exhibits a potential binding site for small molecules that could stabilize the p53/14-3-3 protein complex suggesting the possibility for therapeutic intervention. ..
- Nishino T, Miyazaki M, Hoshino H, Miwa Y, Horinouchi S, Yoshida M. 14-3-3 regulates the nuclear import of class IIa histone deacetylases. Biochem Biophys Res Commun. 2008;377:852-6 pubmed publisher..Phosphorylation-induced 14-3-3 binding biases the balance of nucleo-cytoplasmic shuttling toward the cytoplasm by inhibiting nuclear import. ..
- Krasnianski A, Bartl M, Sanchez Juan P, Heinemann U, Meissner B, Varges D, et al. Fatal familial insomnia: Clinical features and early identification. Ann Neurol. 2008;63:658-61 pubmed publisher..Because the sensitivity of the most diagnostic tests is low in fatal familial insomnia, detailed clinical investigation is extremely important. Polysomnography may help to support the diagnosis. ..
- Kostelecky B, Saurin A, Purkiss A, Parker P, McDonald N. Recognition of an intra-chain tandem 14-3-3 binding site within PKCepsilon. EMBO Rep. 2009;10:983-9 pubmed publisher..This dual-site intra-chain recognition has implications for other 14-3-3 targets, which seem to have only a single 14-3-3 motif, as other lower affinity and cryptic 14-3-3 gatekeeper sites might exist. ..
- Li F, Mofunanya A, Harris K, Takemaru K. Chibby cooperates with 14-3-3 to regulate beta-catenin subcellular distribution and signaling activity. J Cell Biol. 2008;181:1141-54 pubmed publisher..Our results therefore suggest a novel paradigm through which Cby acts in concert with 14-3-3 proteins to facilitate nuclear export of beta-catenin, thereby antagonizing beta-catenin signaling. ..
- Visconti S, Camoni L, Marra M, Aducci P. Role of the 14-3-3 C-terminal region in the interaction with the plasma membrane H+-ATPase. Plant Cell Physiol. 2008;49:1887-97 pubmed publisher..The implications of these findings for a integrated model of 14-3-3 interaction with H(+)-ATPase are discussed. ..
- Neal C, Yao J, Yang W, Zhou X, Nguyen N, Lu J, et al. 14-3-3zeta overexpression defines high risk for breast cancer recurrence and promotes cancer cell survival. Cancer Res. 2009;69:3425-32 pubmed publisher..Therefore, 14-3-3zeta overexpression is a novel molecular marker for disease recurrence in breast cancer patients and may serve as an effective therapeutic target in patients whose tumors overexpress 14-3-3zeta. ..
- Aslan J, You H, Williamson D, Endig J, Youker R, Thomas L, et al. Akt and 14-3-3 control a PACS-2 homeostatic switch that integrates membrane traffic with TRAIL-induced apoptosis. Mol Cell. 2009;34:497-509 pubmed publisher..Together, these studies identify the phosphorylation state of PACS-2 Ser437 as a molecular switch that integrates cellular homeostasis with TRAIL-induced apoptosis. ..
- Nichols R, Dzamko N, Morrice N, Campbell D, Deak M, Ordureau A, et al. 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization. Biochem J. 2010;430:393-404 pubmed publisher..These results provide the first evidence suggesting that 14-3-3 regulates LRRK2 and that disruption of the interaction of LRRK2 with 14-3-3 may be linked to Parkinson's disease...
- Silhan J, Vacha P, Strnadova P, Vecer J, Herman P, Sulc M, et al. 14-3-3 protein masks the DNA binding interface of forkhead transcription factor FOXO4. J Biol Chem. 2009;284:19349-60 pubmed publisher..The model of the complex suggests that the forkhead domain of FOXO4 is docked within the central channel of the 14-3-3 protein dimer, consistent with our hypothesis that 14-3-3 masks the DNA binding interface of FOXO4. ..
- Watkins J, Lewandowski K, Meek S, Storz P, Toker A, Piwnica Worms H. Phosphorylation of the Par-1 polarity kinase by protein kinase D regulates 14-3-3 binding and membrane association. Proc Natl Acad Sci U S A. 2008;105:18378-83 pubmed publisher..Thus, 2 arms of the PKC pathway regulate interactions between Par-1b and 14-3-3 proteins: one involving aPKC and the other nPKC/PKD. ..
- Purwestri Y, Ogaki Y, Tamaki S, Tsuji H, Shimamoto K. The 14-3-3 protein GF14c acts as a negative regulator of flowering in rice by interacting with the florigen Hd3a. Plant Cell Physiol. 2009;50:429-38 pubmed publisher..Since the 14-3-3 protein has been shown to interact with FT protein in tomato and Arabidopsis, our results in rice provide important findings about FT signaling in plants...
- Telles E, Hosing A, Kundu S, Venkatraman P, Dalal S. A novel pocket in 14-3-3epsilon is required to mediate specific complex formation with cdc25C and to inhibit cell cycle progression upon activation of checkpoint pathways. Exp Cell Res. 2009;315:1448-57 pubmed publisher..These results suggest that the specificity of the 14-3-3 ligand interaction may be dependent on structural motifs present in the individual 14-3-3 isoforms. ..
- Han J, Jeong E, Kim Y, Roh G, Kim H, Kang S, et al. C-jun N-terminal kinase regulates the interaction between 14-3-3 and Bad in ethanol-induced cell death. J Neurosci Res. 2008;86:3221-9 pubmed publisher..We hypothesize that JNK may play an important role during ethanol-induced cell death via the inhibition of antiapoptotic function of 14-3-3 as well as activation of proapoptotic function of Bad. ..
- Danes C, Wyszomierski S, Lu J, Neal C, Yang W, Yu D. 14-3-3 zeta down-regulates p53 in mammary epithelial cells and confers luminal filling. Cancer Res. 2008;68:1760-7 pubmed publisher..These data suggest that 14-3-3 zeta overexpression is a critical event in early breast disease, and down-regulation of p53 is one of the mechanisms by which 14-3-3 zeta alters MEC acini structure and increases the risk of breast cancer. ..
- Koga Y, Ikebe M. A novel regulatory mechanism of myosin light chain phosphorylation via binding of 14-3-3 to myosin phosphatase. Mol Biol Cell. 2008;19:1062-71 pubmed..The present study revealed a new RhoA/Rho-kinase-dependent regulatory mechanism of myosin II phosphorylation by 14-3-3 that dissociates MLCP from myosin II and attenuates MLCP activity. ..
- Winter S, Fischle W, Seiser C. Modulation of 14-3-3 interaction with phosphorylated histone H3 by combinatorial modification patterns. Cell Cycle. 2008;7:1336-42 pubmed..Here we discuss the binding of 14-3-3 proteins to histone H3 in detail and putative biological implications of these interactions. ..
- Rajagopalan S, Sade R, Townsley F, Fersht A. Mechanistic differences in the transcriptional activation of p53 by 14-3-3 isoforms. Nucleic Acids Res. 2010;38:893-906 pubmed publisher..We discuss the isoform-specific roles of 14-3-3 in p53 stabilization and activation of specific-DNA binding. ..
- Takemaru K, Fischer V, Li F. Fine-tuning of nuclear-catenin by Chibby and 14-3-3. Cell Cycle. 2009;8:210-3 pubmed..Here, we review recent literature concerning Cby function and discuss our current understanding of the relationship between Wnt and Akt signaling. ..
- Lu J, Guo H, Treekitkarnmongkol W, Li P, Zhang J, Shi B, et al. 14-3-3zeta Cooperates with ErbB2 to promote ductal carcinoma in situ progression to invasive breast cancer by inducing epithelial-mesenchymal transition. Cancer Cell. 2009;16:195-207 pubmed publisher..Importantly, patients whose breast tumors overexpressed both ErbB2 and 14-3-3zeta had higher rates of metastatic recurrence and death than those whose tumors overexpressed only one. ..
- Dibble C, Asara J, Manning B. Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1. Mol Cell Biol. 2009;29:5657-70 pubmed publisher..We provide evidence that Rictor-T1135 phosphorylation acts in parallel with other mTORC1-dependent feedback mechanisms, such as those affecting IRS-1 signaling to PI3K, to regulate the response of Akt to insulin. ..
- Morrison D. The 14-3-3 proteins: integrators of diverse signaling cues that impact cell fate and cancer development. Trends Cell Biol. 2009;19:16-23 pubmed publisher..This review examines the recent advances that further elucidate the role of 14-3-3 proteins as integrators of diverse signaling cues that influence cell fate decisions and tumorigenesis. ..
- Rajagopalan S, Jaulent A, Wells M, Veprintsev D, Fersht A. 14-3-3 activation of DNA binding of p53 by enhancing its association into tetramers. Nucleic Acids Res. 2008;36:5983-91 pubmed publisher..If the in vitro data extrapolate to in vivo, then it is an attractive hypothesis that p53 activity may be subject to control by accessory proteins lowering its tetramer-dimer dissociation constant from its normal value of 120-150 nM. ..
- Dillon R, Brown S, Ling C, Shioda T, Muller W. An EGR2/CITED1 transcription factor complex and the 14-3-3sigma tumor suppressor are involved in regulating ErbB2 expression in a transgenic-mouse model of human breast cancer. Mol Cell Biol. 2007;27:8648-57 pubmed
- Zhao B, Wei X, Li W, Udan R, Yang Q, Kim J, et al. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 2007;21:2747-61 pubmed..Our observations demonstrate that YAP plays a key role in the Hippo pathway to control cell proliferation in response to cell contact. ..
- Faul C, Dhume A, Schecter A, Mundel P. Protein kinase A, Ca2+/calmodulin-dependent kinase II, and calcineurin regulate the intracellular trafficking of myopodin between the Z-disc and the nucleus of cardiac myocytes. Mol Cell Biol. 2007;27:8215-27 pubmed..The identification of myopodin as a direct target of PKA, CaMKII, and calcineurin defines a novel intracellular signaling pathway whereby changes in Z-disc dynamics may translate into compartmentalized signal transduction in the heart. ..
- Mizuno E, Kitamura N, Komada M. 14-3-3-dependent inhibition of the deubiquitinating activity of UBPY and its cancellation in the M phase. Exp Cell Res. 2007;313:3624-34 pubmed..We conclude that UBPY is catalytically inhibited in a phosphorylation-dependent manner by 14-3-3s during the interphase, and this regulation is cancelled in the M phase. ..
- Linde C, Di Leva F, Domi T, Tosatto S, Brini M, Carafoli E. Inhibitory interaction of the 14-3-3 proteins with ubiquitous (PMCA1) and tissue-specific (PMCA3) isoforms of the plasma membrane Ca2+ pump. Cell Calcium. 2008;43:550-61 pubmed
- Winter S, Simboeck E, Fischle W, Zupkovitz G, Dohnal I, Mechtler K, et al. 14-3-3 proteins recognize a histone code at histone H3 and are required for transcriptional activation. EMBO J. 2008;27:88-99 pubmed..Finally, siRNA-mediated loss of 14-3-3 proteins abolishes the transcriptional activation of HDAC1. Together our data indicate that 14-3-3 proteins are crucial mediators of histone phosphoacetylation signals. ..
- Omi K, Hachiya N, Tanaka M, Tokunaga K, Kaneko K. 14-3-3zeta is indispensable for aggregate formation of polyglutamine-expanded huntingtin protein. Neurosci Lett. 2008;431:45-50 pubmed..This indicates that 14-3-3zeta participates in aggregate formation under nonnative conditions. Our data support a novel role for 14-3-3zeta in the aggregate formation of nonnative, aggregation-prone proteins. ..
- Niemantsverdriet M, Wagner K, Visser M, Backendorf C. Cellular functions of 14-3-3 zeta in apoptosis and cell adhesion emphasize its oncogenic character. Oncogene. 2008;27:1315-9 pubmed
- Satoh K, Shirabe S, Tsujino A, Eguchi H, Motomura M, Honda H, et al. Total tau protein in cerebrospinal fluid and diffusion-weighted MRI as an early diagnostic marker for Creutzfeldt-Jakob disease. Dement Geriatr Cogn Disord. 2007;24:207-12 pubmed..Moreover, the data in this study showed that detection of t-tau protein combined with DWI identified 98% of the early-stage cases, and these tests should be included as diagnostic criteria for CJD. ..
- Acevedo S, Tsigkari K, Grammenoudi S, Skoulakis E. In vivo functional specificity and homeostasis of Drosophila 14-3-3 proteins. Genetics. 2007;177:239-53 pubmed..These results demonstrate functional differences both among Drosophila 14-3-3 proteins and between the two LEO isoforms in vivo, which likely underlie differential dimer affinities toward 14-3-3 targets. ..
- Geraghty K, Chen S, Harthill J, Ibrahim A, Toth R, Morrice N, et al. Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR. Biochem J. 2007;407:231-41 pubmed..Thus, although AS160 is a common target of insulin, IGF-1, EGF, PMA and AICAR, these stimuli induce distinctive patterns of phosphorylation and 14-3-3 binding, mediated by at least four protein kinases. ..
- Zannis Hadjopoulos M, Yahyaoui W, Callejo M. 14-3-3 cruciform-binding proteins as regulators of eukaryotic DNA replication. Trends Biochem Sci. 2008;33:44-50 pubmed..Five 14-3-3 protein isoforms (beta, gamma, epsilon, zeta and sigma) have been identified as having cruciform binding activity. ..
- Shiga Y, Satoh K, Kitamoto T, Kanno S, Nakashima I, Sato S, et al. Two different clinical phenotypes of Creutzfeldt-Jakob disease with a M232R substitution. J Neurol. 2007;254:1509-17 pubmed..More studies are needed to determine whether M232R substitution causes the disease and influences the disease progression. ..
- Lee M, Sabapathy K. Phosphorylation at carboxyl-terminal S373 and S375 residues and 14-3-3 binding are not required for mouse p53 function. Neoplasia. 2007;9:690-8 pubmed..Together, the data suggest that despite a high homology with human p53, neither phosphorylation status at S373 and S375 nor 14-3-3 binding may be a critical event for mouse p53 to be functional. ..
- Ryu H, Kim K, Cho H, Park J, Choe S, Hwang I. Nucleocytoplasmic shuttling of BZR1 mediated by phosphorylation is essential in Arabidopsis brassinosteroid signaling. Plant Cell. 2007;19:2749-62 pubmed..We propose that the spatial redistribution of BZR1 is critical for proper BR signaling in plant growth and development. ..
- Gampala S, Kim T, He J, Tang W, Deng Z, Bai M, et al. An essential role for 14-3-3 proteins in brassinosteroid signal transduction in Arabidopsis. Dev Cell. 2007;13:177-89 pubmed..This study demonstrates that multiple mechanisms are required for BR regulation of gene expression and plant growth. ..
- Pereira Faca S, Kuick R, Puravs E, Zhang Q, Krasnoselsky A, Phanstiel D, et al. Identification of 14-3-3 theta as an antigen that induces a humoral response in lung cancer. Cancer Res. 2007;67:12000-6 pubmed..5 proteins previously identified as associated with autoantibodies in lung cancer, gave a sensitivity of 55% at 95% specificity (area under the curve, 0.838) in discriminating lung cancer at the preclinical stage from matched controls. ..
- Tak H, Jang E, Kim S, Park J, Suk J, Yoon Y, et al. 14-3-3epsilon inhibits MK5-mediated cell migration by disrupting F-actin polymerization. Cell Signal. 2007;19:2379-87 pubmed
- Fan T, Li R, Todd N, Qiu Q, Fang H, Wang H, et al. Up-regulation of 14-3-3zeta in lung cancer and its implication as prognostic and therapeutic target. Cancer Res. 2007;67:7901-6 pubmed..008). Our results suggest that 14-3-3zeta is a potential target for developing a prognostic biomarker and therapeutics that can enhance the antitumor activity of cisplatin for NSCLC. ..
- Yang H, Wen Y, Lin Y, Pham L, Su C, Yang H, et al. Roles for negative cell regulator 14-3-3sigma in control of MDM2 activities. Oncogene. 2007;26:7355-62 pubmed..Also, 14-3-3sigma blocks MDM2-mediated retinoblastoma degradation and p53 NEDDylation. Our results provide evidence that 14-3-3sigma is a pivotal MDM2 regulator involved in blocking a variety of activities of MDM2. ..
- Li F, Mofunanya A, Fischer V, Hall J, Takemaru K. Nuclear-cytoplasmic shuttling of Chibby controls beta-catenin signaling. Mol Biol Cell. 2010;21:311-22 pubmed publisher..Taken together, these findings unravel the molecular basis through which a combinatorial action of Cby and 14-3-3 proteins controls the dynamic nuclear-cytoplasmic trafficking of beta-catenin. ..
- Zheng G, Peng F, Ding R, Yu Y, Ouyang Y, Chen Z, et al. Identification of proteins responsible for the multiple drug resistance in 5-fluorouracil-induced breast cancer cell using proteomics analysis. J Cancer Res Clin Oncol. 2010;136:1477-88 pubmed publisher..These findings may provide theoretical support for the prediction of chemotherapeutic response and reverse of MDR. ..
- Eiseler T, Döppler H, Yan I, Kitatani K, Mizuno K, Storz P. Protein kinase D1 regulates cofilin-mediated F-actin reorganization and cell motility through slingshot. Nat Cell Biol. 2009;11:545-56 pubmed publisher..Consequently, expression of constitutively active PKD1 in invasive tumour cells enhanced the phosphorylation of cofilin and effectively blocked the formation of free actin-filament barbed ends and directed cell migration. ..
- Xia S, Xu Y, Xu Q, Xie Z, Shen X, Zhou W, et al. [Analysis for clinical and genetic characteristics of a sporadic FFI case]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2009;23:124-6 pubmed..This patient might be the first SFFI patient reported in China and the case finding might have momentousness in clinical and basical study. ..