This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Iso, T.
Right arrow Articles by Hamamori, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Iso, T.
Right arrow Articles by Hamamori, Y.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2001, p. 6071-6079, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.6071-6079.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

HERP, a New Primary Target of Notch Regulated by Ligand Binding

Tatsuya Iso,1,2 Vittorio Sartorelli,3 Gene Chung,1 Toshiaki Shichinohe,1,4 Larry Kedes,1,2,5,* and Yasuo Hamamori1,2,*

Institute for Genetic Medicine,1 Department of Biochemistry and Molecular Biology,2 Department of Pathology,4 and Department of Medicine,5 Keck School of Medicine of the University of Southern California, Los Angeles, California 90089-9075, and Laboratory of Muscle Biology, Muscle Gene Expression Group, NIAMS-IRP, National Institutes of Health, Bethesda, Maryland 208923

Received 31 January 2001/Returned for modification 19 March 2001/Accepted 21 May 2001

Notch signaling dictates cell fate and critically influences cell proliferation, differentiation, and apoptosis in metazoans. Ligand binding initiates the signal through regulated intramembrane proteolysis of a transmembrane Notch receptor which releases the signal-transducing Notch intracellular domain (NICD). The HES/E(spl) gene family is a primary target of Notch and thus far the only known Notch effector. A newly isolated HERP family, a HES-related basic helix-loop-helix protein family, has been proposed as a potential target of Notch, based on its induction following NICD overexpression. However, NICD is physiologically maintained at an extremely low level that typically escapes detection, and therefore, nonregulated overexpression of NICD---as in transient transfection---has the potential of generating cellular responses of little physiological relevance. Indeed, a constitutively active NICD indiscriminately up-regulates expression of both HERP1 and HERP2 mRNAs. However, physiological Notch stimulation through ligand binding results in the selective induction of HERP2 but not HERP1 mRNA and causes only marginal up-regulation of HES1 mRNA. Importantly, HERP2 is an immediate target gene of Notch signaling since HERP2 mRNA expression is induced even in the absence of de novo protein synthesis. HERP2 mRNA induction is accompanied by specific expression of HERP2 protein in the nucleus. Furthermore, using RBP-Jk-deficient cells, we show that an RBP-Jk protein, a transcription factor that directly activates HES/E(spl) transcription, also is essential for HERP2 mRNA expression and that expression of exogenous RBP-Jk is sufficient to rescue HERP2 mRNA expression. These data establish that HERP2 is a novel primary target gene of Notch that, together with HES, may effect diverse biological activities of Notch.

* Corresponding author. Mailing address for Larry Kedes: 2250 Alcazar St., Los Angeles, CA 90089. Phone: (323) 442-1144. Fax: (323) 442-2764. E-mail: kedes{at}hsc.usc.edu. Present address for Yasuo Hamamori: One Baylor Plaza, 506C, Houston, TX 77030. Phone: (713) 798-3088. Fax: (713) 798-7437. E-mail: hamamori{at}bcm.tmc.edu.

Molecular and Cellular Biology, September 2001, p. 6071-6079, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.6071-6079.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Gould, F., Harrison, S. M., Hewitt, E. W., Whitehouse, A. (2009). Kaposi's Sarcoma-Associated Herpesvirus RTA Promotes Degradation of the Hey1 Repressor Protein through the Ubiquitin Proteasome Pathway. J. Virol. 83: 6727-6738 [Abstract] [Full Text]  
  • Morrow, D., Guha, S., Sweeney, C., Birney, Y., Walshe, T., O'Brien, C., Walls, D., Redmond, E. M., Cahill, P. A. (2008). Notch and Vascular Smooth Muscle Cell Phenotype. Circ. Res. 103: 1370-1382 [Abstract] [Full Text]  
  • Smerdel-Ramoya, A., Zanotti, S., Deregowski, V., Canalis, E. (2008). Connective Tissue Growth Factor Enhances Osteoblastogenesis in Vitro. J. Biol. Chem. 283: 22690-22699 [Abstract] [Full Text]  
  • Kim, M.-Y., Park, J.-H., Mo, J.-S., Ann, E.-J., Han, S.-O., Baek, S.-H., Kim, K.-J., Im, S.-Y., Park, J.-W., Choi, E.-J., Park, H.-S. (2008). Downregulation by lipopolysaccharide of Notch signaling, via nitric oxide. J. Cell Sci. 121: 1466-1476 [Abstract] [Full Text]  
  • Canalis, E. (2008). Notch Signaling in Osteoblasts. Sci Signal 1: pe17-pe17 [Abstract] [Full Text]  
  • Chen, J., Zacharek, A., Li, A., Cui, X., Roberts, C., Lu, M., Chopp, M. (2008). Atorvastatin Promotes Presenilin-1 Expression and Notch1 Activity and Increases Neural Progenitor Cell Proliferation After Stroke. Stroke 39: 220-226 [Abstract] [Full Text]  
  • Fischer, A., Gessler, M. (2007). Delta Notch and then? Protein interactions and proposed modes of repression by Hes and Hey bHLH factors. Nucleic Acids Res 35: 4583-4596 [Abstract] [Full Text]  
  • Xin, M., Small, E. M., van Rooij, E., Qi, X., Richardson, J. A., Srivastava, D., Nakagawa, O., Olson, E. N. (2007). Essential roles of the bHLH transcription factor Hrt2 in repression of atrial gene expression and maintenance of postnatal cardiac function. Proc. Natl. Acad. Sci. USA 104: 7975-7980 [Abstract] [Full Text]  
  • Koibuchi, N., Chin, M. T. (2007). CHF1/Hey2 Plays a Pivotal Role in Left Ventricular Maturation Through Suppression of Ectopic Atrial Gene Expression. Circ. Res. 100: 850-855 [Abstract] [Full Text]  
  • Little, G. H., Bai, Y., Williams, T., Poizat, C. (2007). Nuclear Calcium/Calmodulin-dependent Protein Kinase II{delta} Preferentially Transmits Signals to Histone Deacetylase 4 in Cardiac Cells. J. Biol. Chem. 282: 7219-7231 [Abstract] [Full Text]  
  • Fernandez-Majada, V., Aguilera, C., Villanueva, A., Vilardell, F., Robert-Moreno, A., Aytes, A., Real, F. X., Capella, G., Mayo, M. W., Espinosa, L., Bigas, A. (2007). Nuclear IKK activity leads to dysregulated Notch-dependent gene expression in colorectal cancer. Proc. Natl. Acad. Sci. USA 104: 276-281 [Abstract] [Full Text]  
  • Kawai-Kowase, K., Owens, G. K. (2007). Multiple repressor pathways contribute to phenotypic switching of vascular smooth muscle cells. Am. J. Physiol. Cell Physiol. 292: C59-C69 [Abstract] [Full Text]  
  • Burd, C. J, Morey, L. M, Knudsen, K. E (2006). Androgen receptor corepressors and prostate cancer. Endocr Relat Cancer 13: 979-994 [Abstract] [Full Text]  
  • Rutenberg, J. B., Fischer, A., Jia, H., Gessler, M., Zhong, T. P., Mercola, M. (2006). Developmental patterning of the cardiac atrioventricular canal by Notch and Hairy-related transcription factors. Development 133: 4381-4390 [Abstract] [Full Text]  
  • Doi, H., Iso, T., Sato, H., Yamazaki, M., Matsui, H., Tanaka, T., Manabe, I., Arai, M., Nagai, R., Kurabayashi, M. (2006). Jagged1-selective Notch Signaling Induces Smooth Muscle Differentiation via a RBP-J{kappa}-dependent Pathway. J. Biol. Chem. 281: 28555-28564 [Abstract] [Full Text]  
  • Xiang, F., Sakata, Y., Cui, L., Youngblood, J. M., Nakagami, H., Liao, J. K., Liao, R., Chin, M. T. (2006). Transcription factor CHF1/Hey2 suppresses cardiac hypertrophy through an inhibitory interaction with GATA4. Am. J. Physiol. Heart Circ. Physiol. 290: H1997-H2006 [Abstract] [Full Text]  
  • Watanabe, Y., Kokubo, H., Miyagawa-Tomita, S., Endo, M., Igarashi, K., Aisaki, K. i., Kanno, J., Saga, Y. (2006). Activation of Notch1 signaling in cardiogenic mesoderm induces abnormal heart morphogenesis in mouse. Development 133: 1625-1634 [Abstract] [Full Text]  
  • Williams, C. K., Li, J.-L., Murga, M., Harris, A. L., Tosato, G. (2006). Up-regulation of the Notch ligand Delta-like 4 inhibits VEGF-induced endothelial cell function. Blood 107: 931-939 [Abstract] [Full Text]  
  • Doi, H., Iso, T., Yamazaki, M., Akiyama, H., Kanai, H., Sato, H., Kawai-Kowase, K., Tanaka, T., Maeno, T., Okamoto, E.-i., Arai, M., Kedes, L., Kurabayashi, M. (2005). HERP1 Inhibits Myocardin-Induced Vascular Smooth Muscle Cell Differentiation by Interfering With SRF Binding to CArG Box. Arterioscler. Thromb. Vasc. Bio. 25: 2328-2334 [Abstract] [Full Text]  
  • Limbourg, F. P., Takeshita, K., Radtke, F., Bronson, R. T., Chin, M. T., Liao, J. K. (2005). Essential Role of Endothelial Notch1 in Angiogenesis. Circulation 111: 1826-1832 [Abstract] [Full Text]  
  • Nishikawa, Y., Doi, Y., Watanabe, H., Tokairin, T., Omori, Y., Su, M., Yoshioka, T., Enomoto, K. (2005). Transdifferentiation of Mature Rat Hepatocytes into Bile Duct-Like Cells in Vitro. Am. J. Pathol. 166: 1077-1088 [Abstract] [Full Text]  
  • Belandia, B., Powell, S. M., Garcia-Pedrero, J. M., Walker, M. M., Bevan, C. L., Parker, M. G. (2005). Hey1, a Mediator of Notch Signaling, Is an Androgen Receptor Corepressor. Mol. Cell. Biol. 25: 1425-1436 [Abstract] [Full Text]  
  • Kathiriya, I. S., King, I. N., Murakami, M., Nakagawa, M., Astle, J. M., Gardner, K. A., Gerard, R. D., Olson, E. N., Srivastava, D., Nakagawa, O. (2004). Hairy-related Transcription Factors Inhibit GATA-dependent Cardiac Gene Expression through a Signal-responsive Mechanism. J. Biol. Chem. 279: 54937-54943 [Abstract] [Full Text]  
  • Yeh, T.-S., Hsieh, R.-H., Shen, S.-C., Wang, S.-H., Tseng, M.-J., Shih, C.-M., Lin, J.-J. (2004). Nuclear {beta}II-Tubulin Associates with the Activated Notch Receptor to Modulate Notch Signaling. Cancer Res. 64: 8334-8340 [Abstract] [Full Text]  
  • Sakata, Y., Xiang, F., Chen, Z., Kiriyama, Y., Kamei, C. N., Simon, D. I., Chin, M. T. (2004). Transcription Factor CHF1/Hey2 Regulates Neointimal Formation In Vivo and Vascular Smooth Muscle Proliferation and Migration In Vitro. Arterioscler. Thromb. Vasc. Bio. 24: 2069-2074 [Abstract] [Full Text]  
  • Hoflinger, S., Kesavan, K., Fuxa, M., Hutter, C., Heavey, B., Radtke, F., Busslinger, M. (2004). Analysis of Notch1 Function by In Vitro T Cell Differentiation of Pax5 Mutant Lymphoid Progenitors. J. Immunol. 173: 3935-3944 [Abstract] [Full Text]  
  • Zamurovic, N., Cappellen, D., Rohner, D., Susa, M. (2004). Coordinated Activation of Notch, Wnt, and Transforming Growth Factor-{beta} Signaling Pathways in Bone Morphogenic Protein 2-induced Osteogenesis: Notch TARGET GENE Hey1 INHIBITS MINERALIZATION AND Runx2 TRANSCRIPTIONAL ACTIVITY. J. Biol. Chem. 279: 37704-37715 [Abstract] [Full Text]  
  • Kokubo, H., Miyagawa-Tomita, S., Tomimatsu, H., Nakashima, Y., Nakazawa, M., Saga, Y., Johnson, R. L. (2004). Targeted Disruption of hesr2 Results in Atrioventricular Valve Anomalies That Lead to Heart Dysfunction. Circ. Res. 95: 540-547 [Abstract] [Full Text]  
  • Elagib, K. E., Xiao, M., Hussaini, I. M., Delehanty, L. L., Palmer, L. A., Racke, F. K., Birrer, M. J., Shanmugasundaram, G., McDevitt, M. A., Goldfarb, A. N. (2004). Jun Blockade of Erythropoiesis: Role for Repression of GATA-1 by HERP2. Mol. Cell. Biol. 24: 7779-7794 [Abstract] [Full Text]  
  • Tanimizu, N., Miyajima, A. (2004). Notch signaling controls hepatoblast differentiation by altering the expression of liver-enriched transcription factors. J. Cell Sci. 117: 3165-3174 [Abstract] [Full Text]  
  • Nakatani, T., Mizuhara, E., Minaki, Y., Sakamoto, Y., Ono, Y. (2004). Helt, a Novel Basic-Helix-Loop-Helix Transcriptional Repressor Expressed in the Developing Central Nervous System. J. Biol. Chem. 279: 16356-16367 [Abstract] [Full Text]  
  • Miyoshi, G., Bessho, Y., Yamada, S., Kageyama, R. (2004). Identification of a Novel Basic Helix-Loop-Helix Gene, Heslike, and Its Role in GABAergic Neurogenesis. J. Neurosci. 24: 3672-3682 [Abstract] [Full Text]  
  • Dahlqvist, C., Blokzijl, A., Chapman, G., Falk, A., Dannaeus, K., Ibanez, C. F., Lendahl, U. (2003). Functional Notch signaling is required for BMP4-induced inhibition of myogenic differentiation. Development 130: 6089-6099 [Abstract] [Full Text]  
  • Sakamoto, M., Hirata, H., Ohtsuka, T., Bessho, Y., Kageyama, R. (2003). The Basic Helix-Loop-Helix Genes Hesr1/Hey1 and Hesr2/Hey2 Regulate Maintenance of Neural Precursor Cells in the Brain. J. Biol. Chem. 278: 44808-44815 [Abstract] [Full Text]  
  • Yeh, T.-S., Lin, Y.-M., Hsieh, R.-H., Tseng, M.-J. (2003). Association of Transcription Factor YY1 with the High Molecular Weight Notch Complex Suppresses the Transactivation Activity of Notch. J. Biol. Chem. 278: 41963-41969 [Abstract] [Full Text]  
  • Espinosa, L., Ingles-Esteve, J., Aguilera, C., Bigas, A. (2003). Phosphorylation by Glycogen Synthase Kinase-3{beta} Down-regulates Notch Activity, a Link for Notch and Wnt Pathways. J. Biol. Chem. 278: 32227-32235 [Abstract] [Full Text]  
  • Sakata, Y., Kamei, C. N., Nakagami, H., Bronson, R., Liao, J. K., Chin, M. T. (2002). Ventricular septal defect and cardiomyopathy in mice lacking the transcription factor CHF1/Hey2. Proc. Natl. Acad. Sci. USA 99: 16197-16202 [Abstract] [Full Text]  
  • Wu, L., Sun, T., Kobayashi, K., Gao, P., Griffin, J. D. (2002). Identification of a Family of Mastermind-Like Transcriptional Coactivators for Mammalian Notch Receptors. Mol. Cell. Biol. 22: 7688-7700 [Abstract] [Full Text]  
  • Lemon, W J, Bernert, H, Sun, H, Wang, Y, You, M (2002). Identification of candidate lung cancer susceptibility genes in mouse using oligonucleotide arrays. J. Med. Genet. 39: 644-655 [Abstract] [Full Text]  
  • Yan, B., Raben, N., Plotz, P. (2002). The Human Acid alpha -Glucosidase Gene Is a Novel Target of the Notch-1/Hes-1 Signaling Pathway. J. Biol. Chem. 277: 29760-29764 [Abstract] [Full Text]  
  • Wang, W., Campos, A. H., Prince, C. Z., Mou, Y., Pollman, M. J. (2002). Coordinate Notch3-Hairy-related Transcription Factor Pathway Regulation in Response to Arterial Injury. MEDIATOR ROLE OF PLATELET-DERIVED GROWTH FACTOR AND ERK. J. Biol. Chem. 277: 23165-23171 [Abstract] [Full Text]  
  • Wang, W., Prince, C. Z., Mou, Y., Pollman, M. J. (2002). Notch3 Signaling in Vascular Smooth Muscle Cells Induces c-FLIP Expression via ERK/MAPK Activation. RESISTANCE TO Fas LIGAND-INDUCED APOPTOSIS. J. Biol. Chem. 277: 21723-21729 [Abstract] [Full Text]  
  • Sriuranpong, V., Borges, M. W., Strock, C. L., Nakakura, E. K., Watkins, D. N., Blaumueller, C. M., Nelkin, B. D., Ball, D. W. (2002). Notch Signaling Induces Rapid Degradation of Achaete-Scute Homolog 1. Mol. Cell. Biol. 22: 3129-3139 [Abstract] [Full Text]  
  • FISCHER, A., LEIMEISTER, C., WINKLER, C., SCHUMACHER, N., KLAMT, B., ELMASRI, H., STEIDL, C., MAIER, M., KNOBELOCH, K.-P., AMANN, K., HELISCH, A., SENDTNER, M., GESSLER, M. (2002). Hey bHLH Factors in Cardiovascular Development. Cold Spring Harb Symp Quant Biol 67: 63-70 [Abstract]  
  • Iso, T., Sartorelli, V., Poizat, C., Iezzi, S., Wu, H.-Y., Chung, G., Kedes, L., Hamamori, Y. (2001). HERP, a Novel Heterodimer Partner of HES/E(spl) in Notch Signaling. Mol. Cell. Biol. 21: 6080-6089 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»