Gene Symbol: Taz
Description: tafazzin
Alias: 5031411C02Rik, 9130012G04Rik, AW107266, AW552613, G4.5, tafazzin
Species: mouse
Products:     Taz

Top Publications

  1. Lu B, Kelher M, Lee D, Lewin T, Coleman R, Choy P, et al. Complex expression pattern of the Barth syndrome gene product tafazzin in human cell lines and murine tissues. Biochem Cell Biol. 2004;82:569-76 pubmed
    ..Only two tafazzin transcripts, both lacking exon 5, were expressed in murine tissues, whereas four tafazzin transcripts, all ..
  2. Varelas X, Miller B, Sopko R, Song S, Gregorieff A, Fellouse F, et al. The Hippo pathway regulates Wnt/beta-catenin signaling. Dev Cell. 2010;18:579-91 pubmed publisher
    ..Here, we show that the Hippo pathway restricts Wnt/beta-Catenin signaling by promoting an interaction between TAZ and DVL in the cytoplasm...
  3. Acehan D, Vaz F, Houtkooper R, James J, Moore V, Tokunaga C, et al. Cardiac and skeletal muscle defects in a mouse model of human Barth syndrome. J Biol Chem. 2011;286:899-908 pubmed publisher
    Barth syndrome is an X-linked genetic disorder caused by mutations in the tafazzin (taz) gene and characterized by dilated cardiomyopathy, exercise intolerance, chronic fatigue, delayed growth, and neutropenia...
  4. Varelas X, Samavarchi Tehrani P, Narimatsu M, Weiss A, Cockburn K, Larsen B, et al. The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-?-SMAD pathway. Dev Cell. 2010;19:831-44 pubmed publisher
    ..cell density information to control tissue growth by regulating the localization of the transcriptional regulators TAZ and YAP (TAZ/YAP)...
  5. Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, et al. Role of YAP/TAZ in mechanotransduction. Nature. 2011;474:179-83 pubmed publisher
    ..Here we report the identification of the Yorkie-homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1) as nuclear relays of mechanical signals ..
  6. Hong J, Hwang E, McManus M, Amsterdam A, Tian Y, Kalmukova R, et al. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science. 2005;309:1074-8 pubmed
    ..Here we report that a 14-3-3-binding protein, TAZ (transcriptional coactivator with PDZ-binding motif), coactivates Runx2-dependent gene transcription while ..
  7. Kiebish M, Yang K, Liu X, Mancuso D, Guan S, Zhao Z, et al. Dysfunctional cardiac mitochondrial bioenergetic, lipidomic, and signaling in a murine model of Barth syndrome. J Lipid Res. 2013;54:1312-25 pubmed publisher
    Barth syndrome is a complex metabolic disorder caused by mutations in the mitochondrial transacylase tafazzin. Recently, an inducible tafazzin shRNA knockdown mouse model was generated to deconvolute the complex bioenergetic phenotype of ..
  8. Soustek M, Falk D, Mah C, Toth M, Schlame M, Lewin A, et al. Characterization of a transgenic short hairpin RNA-induced murine model of Tafazzin deficiency. Hum Gene Ther. 2011;22:865-71 pubmed publisher
    Barth's syndrome (BTHS) is an X-linked mitochondrial disease that is due to a mutation in the Tafazzin (TAZ) gene...
  9. Jang E, Jeong H, Han K, Kwon H, Hong J, Hwang E. TAZ suppresses NFAT5 activity through tyrosine phosphorylation. Mol Cell Biol. 2012;32:4925-32 pubmed publisher
    Transcriptional coactivator with PDZ-binding motif (TAZ) physically interacts with a variety of transcription factors and modulates their activities involved in cell proliferation and mesenchymal stem cell differentiation...

More Information


  1. Powers C, Huang Y, Strauss A, Khuchua Z. Diminished Exercise Capacity and Mitochondrial bc1 Complex Deficiency in Tafazzin-Knockdown Mice. Front Physiol. 2013;4:74 pubmed publisher
    ..The causative gene is the mitochondrial acyl-transferase, tafazzin, that is essential for remodeling acyl chains of cardiolipin...
  2. Liu F, Lagares D, Choi K, Stopfer L, Marinković A, Vrbanac V, et al. Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis. Am J Physiol Lung Cell Mol Physiol. 2015;308:L344-57 pubmed publisher
    ..yes-associated protein (YAP) (homolog of drosophila Yki) and transcriptional coactivator with PDZ-binding motif (TAZ) (also known as Wwtr1), transcriptional effectors of the Hippo pathway, as key matrix stiffness-regulated ..
  3. Poitelon Y, Lopez Anido C, Catignas K, Berti C, Palmisano M, Williamson C, et al. YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells. Nat Neurosci. 2016;19:879-87 pubmed publisher
    ..Yap and Taz are effectors of the Hippo pathway that integrate chemical and mechanical signals in cells...
  4. Galli G, Carrara M, Yuan W, Valdes Quezada C, Gurung B, Pepe Mooney B, et al. YAP Drives Growth by Controlling Transcriptional Pause Release from Dynamic Enhancers. Mol Cell. 2015;60:328-37 pubmed publisher
    ..Our results here uncover the molecular mechanisms employed by YAP to exert its growth and oncogenic functions, and suggest strategies for intervention. ..
  5. Cadalbert L, Ghaffar F, Stevenson D, Bryson S, Vaz F, Gottlieb E, et al. Mouse Tafazzin Is Required for Male Germ Cell Meiosis and Spermatogenesis. PLoS ONE. 2015;10:e0131066 pubmed publisher
    ..Mutation in the Taz gene in Xq28 is thought to be responsible for the condition, by altering mitochondrial lipid content and ..
  6. Yim H, Sung C, You J, Tian Y, Benjamin T. Nek1 and TAZ interact to maintain normal levels of polycystin 2. J Am Soc Nephrol. 2011;22:832-7 pubmed publisher
    ..PKD can also arise from loss of the protein TAZ, an adaptor protein in the E3 ubiquitin ligase complex that targets the ciliary protein polycystin 2 (PC2) for ..
  7. Otsubo K, Goto H, Nishio M, Kawamura K, Yanagi S, Nishie W, et al. MOB1-YAP1/TAZ-NKX2.1 axis controls bronchioalveolar cell differentiation, adhesion and tumour formation. Oncogene. 2017;36:4201-4211 pubmed publisher
    ..Their alveolar epithelial cells showed increased proliferation, impaired YAP1/TAZ-dependent differentiation and decreased surfactant protein production, all features characteristic of human ..
  8. Hsu P, Liu X, Zhang J, Wang H, Ye J, Shi Y. Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy. Autophagy. 2015;11:643-52 pubmed publisher
    b>Tafazzin (TAZ) is a phospholipid transacylase that catalyzes the remodeling of cardiolipin, a mitochondrial phospholipid required for oxidative phosphorylation...
  9. Szczepanek K, Allegood J, Aluri H, Hu Y, Chen Q, Lesnefsky E. Acquired deficiency of tafazzin in the adult heart: Impact on mitochondrial function and response to cardiac injury. Biochim Biophys Acta. 2016;1861:294-300 pubmed publisher
    ..b>Tafazzin (Taz) is an enzyme responsible for remodeling of immature CL containing mixed acyl groups into the mature ..
  10. Singh A, Ramesh S, Cibi D, Yun L, Li J, Li L, et al. Hippo Signaling Mediators Yap and Taz Are Required in the Epicardium for Coronary Vasculature Development. Cell Rep. 2016;15:1384-1393 pubmed publisher
    ..of genetic and pharmacological approaches, we demonstrate that inhibition of Hippo signaling mediators Yap and Taz leads to impaired epicardial epithelial-to-mesenchymal transition (EMT) and a reduction in epicardial cell ..
  11. Panciera T, Azzolin L, Fujimura A, Di Biagio D, Frasson C, Bresolin S, et al. Induction of Expandable Tissue-Specific Stem/Progenitor Cells through Transient Expression of YAP/TAZ. Cell Stem Cell. 2016;19:725-737 pubmed publisher
    ..Here we show that transient expression of exogenous YAP or its closely related paralogue TAZ in primary differentiated mouse cells can induce conversion to a tissue-specific stem/progenitor cell state...
  12. Soustek M, Baligand C, Falk D, Walter G, Lewin A, Byrne B. Endurance training ameliorates complex 3 deficiency in a mouse model of Barth syndrome. J Inherit Metab Dis. 2015;38:915-22 pubmed publisher
    ..is an X-linked metabolic disorder that causes cardiomyopathy in infancy and is linked to mutations within the Tafazzin (TAZ) gene...
  13. Diepenbruck M, Waldmeier L, Ivanek R, Berninger P, Arnold P, van Nimwegen E, et al. Tead2 expression levels control the subcellular distribution of Yap and Taz, zyxin expression and epithelial-mesenchymal transition. J Cell Sci. 2014;127:1523-36 pubmed publisher
    ..Tead transcription factors and their transcriptional co-activators Yap and Taz have been previously implicated in promoting an EMT; however, their direct transcriptional target genes and their ..
  14. Wang G, McCain M, Yang L, He A, Pasqualini F, Agarwal A, et al. Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies. Nat Med. 2014;20:616-23 pubmed publisher
    ..the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation of the gene encoding tafazzin (TAZ)...
  15. Serinagaoglu Y, Paré J, Giovannini M, Cao X. Nf2-Yap signaling controls the expansion of DRG progenitors and glia during DRG development. Dev Biol. 2015;398:97-109 pubmed publisher
    ..The key effectors of this pathway, transcriptional coactivators Yap and Taz, are expressed in DRG progenitors and glia during DRG development but are at least partially inhibited from ..
  16. Bhat K, Salazar K, Balasubramaniyan V, Wani K, Heathcock L, Hollingsworth F, et al. The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma. Genes Dev. 2011;25:2594-609 pubmed publisher
    ..including The Cancer Genome Atlas (TCGA), we identified the transcriptional coactivator with PDZ-binding motif (TAZ), to be highly associated with the MES network...
  17. Ramjee V, Li D, Manderfield L, Liu F, Engleka K, Aghajanian H, et al. Epicardial YAP/TAZ orchestrate an immunosuppressive response following myocardial infarction. J Clin Invest. 2017;127:899-911 pubmed publisher
    ..Mice deficient in epicardial YAP and TAZ, two core Hippo pathway effectors, developed profound post-MI pericardial inflammation and myocardial fibrosis, ..
  18. Tian Y, Kolb R, Hong J, Carroll J, Li D, You J, et al. TAZ promotes PC2 degradation through a SCFbeta-Trcp E3 ligase complex. Mol Cell Biol. 2007;27:6383-95 pubmed
    Studies of a TAZ knockout mouse reveal a novel function of the transcriptional regulator TAZ, that is, as a binding partner of the F-box protein beta-Trcp. TAZ-/- mice develop polycystic kidney disease (PKD) and emphysema...
  19. Zanconato F, Forcato M, Battilana G, Azzolin L, Quaranta E, Bodega B, et al. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nat Cell Biol. 2015;17:1218-27 pubmed publisher
    YAP/TAZ are nuclear effectors of the Hippo pathway regulating organ growth and tumorigenesis. Yet, their function as transcriptional regulators remains underinvestigated...
  20. Finch Edmondson M, Strauss R, Passman A, Sudol M, Yeoh G, Callus B. TAZ Protein Accumulation Is Negatively Regulated by YAP Abundance in Mammalian Cells. J Biol Chem. 2015;290:27928-38 pubmed publisher
    ..YAP and TAZ are transcriptional coactivators that function as effectors of this signaling pathway...
  21. Lee M, Byun M, Furutani Seiki M, Hong J, Jung H. YAP and TAZ regulate skin wound healing. J Invest Dermatol. 2014;134:518-525 pubmed publisher
    ..coactivators in this pathway, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), mediate the major gene regulation and biological functions of the Hippo pathway...
  22. Nguyen A, Xiao B, Neppl R, Kallin E, Li J, Chen T, et al. DOT1L regulates dystrophin expression and is critical for cardiac function. Genes Dev. 2011;25:263-74 pubmed publisher
    ..In addition, our study may open new avenues for the diagnosis and treatment of human heart disease. ..
  23. Ukita M, Yamaguchi T, Ohata N, Tamura M. Sclerostin Enhances Adipocyte Differentiation in 3T3-L1 Cells. J Cell Biochem. 2016;117:1419-28 pubmed publisher
    ..Recently, the transcriptional modulator TAZ has been involved in the canonical Wnt signaling pathway...
  24. Chang C, Goel H, Gao H, Pursell B, Shultz L, Greiner D, et al. A laminin 511 matrix is regulated by TAZ and functions as the ligand for the α6Bβ1 integrin to sustain breast cancer stem cells. Genes Dev. 2015;29:1-6 pubmed publisher
    ..promotes self-renewal and tumor initiation by engaging the α6Bβ1 integrin and activating the Hippo transducer TAZ. Although TAZ is important for the function of breast CSCs, the mechanism is unknown...
  25. Heidary Arash E, Song K, Song S, Shiban A, Attisano L. Arhgef7 promotes activation of the Hippo pathway core kinase Lats. EMBO J. 2014;33:2997-3011 pubmed publisher
    ..kinases, which phosphorylate and promote cytoplasmic localization of the transcriptional regulators Yap and Taz to inhibit transcription...
  26. Acehan D, Khuchua Z, Houtkooper R, Malhotra A, Kaufman J, Vaz F, et al. Distinct effects of tafazzin deletion in differentiated and undifferentiated mitochondria. Mitochondrion. 2009;9:86-95 pubmed publisher
    b>Tafazzin is a conserved mitochondrial protein that is required to maintain normal content and composition of cardiolipin...
  27. Ostojic O, O Leary M, Singh K, Menzies K, Vainshtein A, Hood D. The effects of chronic muscle use and disuse on cardiolipin metabolism. J Appl Physiol (1985). 2013;114:444-52 pubmed publisher
    ..CL synthesis enzymes cardiolipin synthase (CLS) and CTP:PA-cytidylyltransferase-1 (CDS-1); 2) remodeling enzymes tafazzin and acyl-CoA:lysocardiolipin acyltransferase-1 (ALCAT1); and 3) outer membrane CL enzymes, mitochondrial ..
  28. Miranda M, Bialik J, Speight P, Dan Q, Yeung T, Szaszi K, et al. TGF-?1 regulates the expression and transcriptional activity of TAZ protein via a Smad3-independent, myocardin-related transcription factor-mediated mechanism. J Biol Chem. 2017;292:14902-14920 pubmed publisher
    Hippo pathway transcriptional coactivators TAZ and YAP and the TGF-?1 (TGF?) effector Smad3 regulate a common set of genes, can physically interact, and exhibit multilevel cross-talk regulating cell fate-determining and fibrogenic ..
  29. Rivella S, Tamanini F, Bione S, Mancini M, Herman G, Chatterjee A, et al. A comparative transcriptional map of a region of 250 kb on the human and mouse X chromosome between the G6PD and the FLN1 genes. Genomics. 1995;28:377-82 pubmed
    ..The very high conservation that we have described suggests that a potent selective pressure has contributed to such conservation of gene organization. ..
  30. Enger T, Samad Zadeh A, Bouchie M, Skarstein K, Galtung H, Mera T, et al. The Hippo signaling pathway is required for salivary gland development and its dysregulation is associated with Sjogren's syndrome. Lab Invest. 2013;93:1203-18 pubmed publisher
    ..During SMG development, a Hippo pathway effector, TAZ, becomes increasingly phosphorylated and associated with E-cadherin and ?-catenin, consistent with the activation ..
  31. Kwan J, Sczaniecka A, Heidary Arash E, Nguyen L, Chen C, Ratkovic S, et al. DLG5 connects cell polarity and Hippo signaling protein networks by linking PAR-1 with MST1/2. Genes Dev. 2016;30:2696-2709 pubmed publisher
    ..Dlg5 also interacts genetically with Hippo effectors Yap1/Taz Mechanistically, we show that DLG5 inhibits the association between MST1/2 and large tumor suppressor homologs 1/2 (..
  32. Claypool S, Whited K, Srijumnong S, Han X, Koehler C. Barth syndrome mutations that cause tafazzin complex lability. J Cell Biol. 2011;192:447-62 pubmed publisher
    ..The X-linked disease Barth syndrome (BTHS) is caused by mutations in the tafazzin gene TAZ1...
  33. Grove M, Kim H, Santerre M, Krupka A, Han S, Zhai J, et al. YAP/TAZ initiate and maintain Schwann cell myelination. elife. 2017;6: pubmed publisher
    Nuclear exclusion of the transcriptional regulators and potent oncoproteins, YAP/TAZ, is considered necessary for adult tissue homeostasis...
  34. Park H, Kim Y, Yu B, Moroishi T, Mo J, Plouffe S, et al. Alternative Wnt Signaling Activates YAP/TAZ. Cell. 2015;162:780-94 pubmed publisher
    The transcriptional co-activators YAP and TAZ are key regulators of organ size and tissue homeostasis, and their dysregulation contributes to human cancer...
  35. Azzolin L, Zanconato F, Bresolin S, Forcato M, Basso G, Bicciato S, et al. Role of TAZ as mediator of Wnt signaling. Cell. 2012;151:1443-56 pubmed publisher
    ..Here, we report that TAZ, a biologically potent transcriptional coactivator, serves as a downstream element of the Wnt/?-catenin cascade...
  36. Phoon C, Acehan D, Schlame M, Stokes D, Edelman Novemsky I, Yu D, et al. Tafazzin knockdown in mice leads to a developmental cardiomyopathy with early diastolic dysfunction preceding myocardial noncompaction. J Am Heart Assoc. 2012;1: pubmed publisher
    Barth syndrome is a rare, multisystem disorder caused by mutations in tafazzin that lead to cardiolipin deficiency and mitochondrial abnormalities. Patients most commonly develop an early-onset cardiomyopathy in infancy or fetal life...
  37. Tang Y, Feinberg T, Keller E, Li X, Weiss S. Snail/Slug binding interactions with YAP/TAZ control skeletal stem cell self-renewal and differentiation. Nat Cell Biol. 2016;18:917-29 pubmed publisher
    ..Snail/Slug regulate SSC function by forming complexes with the transcriptional co-activators YAP and TAZ in tandem with the inhibition of the Hippo-pathway-dependent regulation of YAP/TAZ signalling cascades...
  38. Wang J, Xiao Y, Hsu C, Martinez Traverso I, Zhang M, Bai Y, et al. Yap and Taz play a crucial role in neural crest-derived craniofacial development. Development. 2016;143:504-15 pubmed publisher
    ..We used the Wnt1(Cre) and Wnt1(Cre2SOR) drivers to conditionally ablate both Yap and Taz in the CNC of mice...
  39. Imajo M, Ebisuya M, Nishida E. Dual role of YAP and TAZ in renewal of the intestinal epithelium. Nat Cell Biol. 2015;17:7-19 pubmed publisher
    ..Here we show, by using intestine-specific gene transfer (iGT), that Hippo signalling effectors, YAP and TAZ, promote both the proliferation of intestinal stem/progenitor cells and their differentiation into goblet cells...
  40. Jeong H, Bae S, An S, Byun M, Hwang J, Yaffe M, et al. TAZ as a novel enhancer of MyoD-mediated myogenic differentiation. FASEB J. 2010;24:3310-20 pubmed publisher
    ..b>TAZ (transcriptional coactivator with PDZ-binding motif) has been characterized as a modulator of mesenchymal stem cell ..
  41. Men T, Piao S, Teng C. [Regulation of differentiation of mesenchymal stem cells by the Hippo pathway effectors TAZ/YAP]. Yi Chuan. 2013;35:1283-90 pubmed
    ..MSCs through regulating the activity of line- age-specific transcription factors by the Hippo pathway effectors Tafazzin (TAZ) and/or Yes-associated protein (YAP)...
  42. Castro D, Martynoga B, Parras C, Ramesh V, Pacary E, Johnston C, et al. A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets. Genes Dev. 2011;25:930-45 pubmed publisher
  43. Huraskin D, Eiber N, Reichel M, Zidek L, Kravic B, Bernkopf D, et al. Wnt/?-catenin signaling via Axin2 is required for myogenesis and, together with YAP/Taz and Tead1, active in IIa/IIx muscle fibers. Development. 2016;143:3128-42 pubmed publisher
    ..In the same fibers, immunofluorescence staining for YAP/Taz and Tead1 was detected. Wnt/?-catenin signaling was absent in quiescent and activated satellite cells...
  44. Bertero T, Cottrill K, Annis S, Bhat B, Gochuico B, Osorio J, et al. A YAP/TAZ-miR-130/301 molecular circuit exerts systems-level control of fibrosis in a network of human diseases and physiologic conditions. Sci Rep. 2015;5:18277 pubmed publisher
    ..of extracellular matrix (ECM) stiffening by the mechanosensitive microRNA-130/301 family, as activated by the YAP/TAZ co-transcription factors, in promoting pulmonary hypertension (PH)...
  45. Li H, Gumbiner B. Deregulation of the Hippo pathway in mouse mammary stem cells promotes mammary tumorigenesis. Mamm Genome. 2016;27:556-564 pubmed
    ..It is a kinase cascade that inhibits the nuclear localization and transcriptional activities of YAP and TAZ. E-cadherin, cell junctions, polarity proteins, and the merlin/NF2 tumor suppressor activate the pathway to inhibit ..
  46. Liu Y, Xin Y, Ye F, Wang W, Lu Q, Kaplan H, et al. Taz-tead1 links cell-cell contact to zeb1 expression, proliferation, and dedifferentiation in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2010;51:3372-8 pubmed publisher
    ..This pathway regulates activity of the Yap and Taz transcription factors, which link epithelial-mesenchymal transition (EMT) to cell proliferation...
  47. Aprikyan A, Khuchua Z. Advances in the understanding of Barth syndrome. Br J Haematol. 2013;161:330-8 pubmed publisher
    ..deletion or substitution mutations in the TAZ gene that appear to result in loss-of-function of the gene product tafazzin. Molecular mechanisms triggering neutropenia and cardiomyopathy in BTHS remain largely unclear...
  48. Kim J, Kwak H, Cha J, Jeong Y, Rhee S, Cheon H. The role of prolyl hydroxylase domain protein (PHD) during rosiglitazone-induced adipocyte differentiation. J Biol Chem. 2014;289:2755-64 pubmed publisher
    ..levels of anti-adipogenic proteins such as GATA-3, KLF-2, and transcriptional coactivator with PDZ binding motif (TAZ), with their reduced ubiquitination, suggesting that PHDs evoke the ubiquitination/proteasomal degradation of anti-..
  49. Han D, Byun S, Park S, Kim J, Kim I, Ha S, et al. YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner. Biochem Biophys Res Commun. 2015;458:110-6 pubmed publisher
    ..Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental ..
  50. Elbediwy A, Vincent Mistiaen Z, Spencer Dene B, Stone R, Boeing S, Wculek S, et al. Integrin signalling regulates YAP and TAZ to control skin homeostasis. Development. 2016;143:1674-87 pubmed publisher
    ..Here, we show that the transcription regulators YAP and TAZ localise to the nucleus in the basal layer of skin and are elevated upon wound healing...
  51. Yang J, Cho S, An J, Jung J, Kim S, Kim S, et al. Osteoblast-targeted overexpression of TAZ increases bone mass in vivo. PLoS ONE. 2013;8:e56585 pubmed publisher
    ..Transcriptional coactivator with a PDZ-binding motif (TAZ) is a transcriptional coactivator that induces differentiation of mesenchymal cells into osteoblasts while blocking ..