Functional Interaction between SEL-10, an F-box Protein, and the Nuclear Form of Activated Notch1 Receptor^*

Neetu Gupta-Rossi, Odile Le Bail, Hedva Gonen^§, Christel Brou, Frédérique Logeat, Emmanuelle Six, Aaron Ciechanover^§, and Alain Israël^¶

From the Unité de Biologie Moléculaire de l'Expression Génique, FRE 2364, CNRS, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France, and the ^§ Department of Biochemistry, Faculty of Medicine, Technion-Israel Institute of Technology, P. O. Box 9649, Haifa 31096, Israel

The Notch signaling pathway is essential in many cell fate decisions in invertebrates as well as in vertebrates. After ligand binding, a two-step proteolytic cleavage releases the intracellular part of the receptor which translocates to the nucleus and acts as a transcriptional activator. Although Notch-induced transcription of genes has been reported extensively, its endogenous nuclear form has been seldom visualized. We report that the nuclear intracellular domain of Notch1 is stabilized by proteasome inhibitors and is a substrate for polyubiquitination in vitro. SEL-10, an F-box protein of the Cdc4 family, was isolated in a genetic screen for Lin12/Notch-negative regulators in Caenorhabditis elegans. We isolated human and murine counterparts of SEL-10 and investigated the role of a dominant-negative form of this protein, deleted of the F-box, on Notch1 stability and activity. This molecule could stabilize intracellular Notch1 and enhance its transcriptional activity but had no effect on inactive membrane-anchored forms of the receptor. We then demonstrated that SEL-10 specifically interacts with nuclear forms of Notch1 and that this interaction requires a phosphorylation event. Taken together, these data suggest that SEL-10 is involved in shutting off Notch signaling by ubiquitin-proteasome-mediated degradation of the active transcriptional factor after a nuclear phosphorylation event.

---

^* This work was supported in part by grants from the Association pour la Recherche contre le Cancer (to A. I.) and by TMR Grant CT 960026 from EC (to A. I. and A. C.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of a postdoctoral fellowship award from EC (Biomed program).

^¶ To whom correspondence should be addressed. E-mail: aisrael@pasteur.fr.

---

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

Notch cooperates with Lozenge/Runx to lock haemocytes into a differentiation programme.

A. Terriente-Felix, J. Li, S. Collins, A. Mulligan, I. Reekie, F. Bernard, A. Krejci, and S. Bray (2013)
Development 140, 926-937
 |  Abstract »  |  Full Text »  |  PDF »

SEL-10/Fbw7-dependent negative feedback regulation of LIN-45/Braf signaling in C. elegans via a conserved phosphodegron.

C. de la Cova and I. Greenwald (2012)
Genes & Dev. 26, 2524-2535
 |  Abstract »  |  Full Text »  |  PDF »

The Matricellular Protein CCN1/Cyr61 Is a Critical Regulator of Sonic Hedgehog in Pancreatic Carcinogenesis.

I. Haque, A. De, M. Majumder, S. Mehta, D. McGregor, S. K. Banerjee, P. Van Veldhuizen, and S. Banerjee (2012)
J. Biol. Chem. 287, 38569-38579
 |  Abstract »  |  Full Text »  |  PDF »

Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma.

M. J. Kiel, T. Velusamy, B. L. Betz, L. Zhao, H. G. Weigelin, M. Y. Chiang, D. R. Huebner-Chan, N. G. Bailey, D. T. Yang, G. Bhagat, et al. (2012)
J. Exp. Med. 209, 1553-1565
 |  Abstract »  |  Full Text »  |  PDF »

Presenilin-2 regulates the degradation of RBP-Jk protein through p38 mitogen-activated protein kinase.

S.-M. Kim, M.-Y. Kim, E.-J. Ann, J.-S. Mo, J.-H. Yoon, and H.-S. Park (2012)
J. Cell Sci. 125, 1296-1308
 |  Abstract »  |  Full Text »  |  PDF »

Notch Signaling Is Antagonized by SAO-1, a Novel GYF-Domain Protein That Interacts with the E3 Ubiquitin Ligase SEL-10 in Caenorhabditis elegans.

V. A. Hale, E. L. Guiney, L. Y. Goldberg, J. H. Haduong, C. S. Kwartler, K. W. Scangos, and C. Goutte (2012)
Genetics 190, 1043-1057
 |  Abstract »  |  Full Text »  |  PDF »

Dual Regulation of Notch1 Signaling Pathway by Adaptor Protein Fe65.

M.-Y. Kim, J.-S. Mo, E.-J. Ann, J.-H. Yoon, and H.-S. Park (2012)
J. Biol. Chem. 287, 4690-4701
 |  Abstract »  |  Full Text »  |  PDF »

Sequential mutations in Notch1, Fbxw7, and Tp53 in radiation-induced mouse thymic lymphomas.

K.-Y. Jen, I. Y. Song, K. L. Banta, D. Wu, J.-H. Mao, and A. Balmain (2012)
Blood 119, 805-809
 |  Abstract »  |  Full Text »  |  PDF »

Notch signaling: simplicity in design, versatility in function.

E. R. Andersson, R. Sandberg, and U. Lendahl (2011)
Development 138, 3593-3612
 |  Abstract »  |  Full Text »  |  PDF »

Hierarchical Phosphorylation within the Ankyrin Repeat Domain Defines a Phosphoregulatory Loop That Regulates Notch Transcriptional Activity.

P. Ranganathan, R. Vasquez-Del Carpio, F. M. Kaplan, H. Wang, A. Gupta, J. D. VanWye, and A. J. Capobianco (2011)
J. Biol. Chem. 286, 28844-28857
 |  Abstract »  |  Full Text »  |  PDF »

Regulation of Notch1 signaling by the APP intracellular domain facilitates degradation of the Notch1 intracellular domain and RBP-Jk.

M.-Y. Kim, J.-S. Mo, E.-J. Ann, J.-H. Yoon, J. Jung, Y.-H. Choi, S.-M. Kim, H.-Y. Kim, J.-S. Ahn, H. Kim, et al. (2011)
J. Cell Sci. 124, 1831-1843
 |  Abstract »  |  Full Text »  |  PDF »

The Adaptor-associated Kinase 1, AAK1, Is a Positive Regulator of the Notch Pathway.

N. Gupta-Rossi, S. Ortica, V. Meas-Yedid, S. Heuss, J. Moretti, J.-C. Olivo-Marin, and A. Israel (2011)
J. Biol. Chem. 286, 18720-18730
 |  Abstract »  |  Full Text »  |  PDF »

Nucleolar Targeting of the Fbw7 Ubiquitin Ligase by a Pseudosubstrate and Glycogen Synthase Kinase 3.

M. Welcker, E. A. Larimore, L. Frappier, and B. E. Clurman (2011)
Mol. Cell. Biol. 31, 1214-1224
 |  Abstract »  |  Full Text »  |  PDF »

Serum- and glucocorticoid-inducible kinase 1 (SGK1) controls Notch1 signaling by downregulation of protein stability through Fbw7 ubiquitin ligase.

J.-S. Mo, E.-J. Ann, J.-H. Yoon, J. Jung, Y.-H. Choi, H.-Y. Kim, J.-S. Ahn, S.-M. Kim, M.-Y. Kim, J.-A. Hong, et al. (2011)
J. Cell Sci. 124, 100-112
 |  Abstract »  |  Full Text »  |  PDF »

Delivering the Lateral Inhibition Punchline: It's All About the Timing.

J. D. Axelrod (2010)
Science Signaling 3, pe38
 |  Abstract »  |  Full Text »  |  PDF »

Notch signaling contributes to proliferation and tumor formation of human T-cell leukemia virus type 1-associated adult T-cell leukemia.

J. Pancewicz, J. M. Taylor, A. Datta, H. H. Baydoun, T. A. Waldmann, O. Hermine, and C. Nicot (2010)
PNAS 107, 16619-16624
 |  Abstract »  |  Full Text »  |  PDF »

Ectodomain Shedding of Interleukin-2 Receptor {beta} and Generation of an Intracellular Functional Fragment.

P. M. de Oca B., V. Malarde, R. Proust, A. Dautry-Varsat, and F. Gesbert (2010)
J. Biol. Chem. 285, 22050-22058
 |  Abstract »  |  Full Text »  |  PDF »

Error Minimization in Lateral Inhibition Circuits.

O. Barad, D. Rosin, E. Hornstein, and N. Barkai (2010)
Science Signaling 3, ra51
 |  Abstract »  |  Full Text »  |  PDF »

Cyclin E Is Stabilized in Response to Replication Fork Barriers Leading to Prolonged S Phase Arrest.

X. Lu, J. Liu, and R. J. Legerski (2009)
J. Biol. Chem. 284, 35325-35337
 |  Abstract »  |  Full Text »  |  PDF »

Artemis Regulates Cell Cycle Recovery from the S Phase Checkpoint by Promoting Degradation of Cyclin E.

H. Wang, X. Zhang, L. Geng, L. Teng, and R. J. Legerski (2009)
J. Biol. Chem. 284, 18236-18243
 |  Abstract »  |  Full Text »  |  PDF »

Notch Signaling and Cancer.

T. Dai (2009)
Am. Assoc. Cancer Res. Educ. Book 2009, 71-79
 |  Full Text »  |  PDF »

Opposite Effects of Notch-1 and Notch-2 on Mesothelioma Cell Survival under Hypoxia Are Exerted through the Akt Pathway.

I. Graziani, S. Eliasz, M. A. De Marco, Y. Chen, H. I. Pass, R. M. De May, P. R. Strack, L. Miele, and M. Bocchetta (2008)
Cancer Res. 68, 9678-9685
 |  Abstract »  |  Full Text »  |  PDF »

Metalloproteinase- and {gamma}-Secretase-mediated Cleavage of Protein-tyrosine Phosphatase Receptor Type Z.

J. P. H. Chow, A. Fujikawa, H. Shimizu, R. Suzuki, and M. Noda (2008)
J. Biol. Chem. 283, 30879-30889
 |  Abstract »  |  Full Text »  |  PDF »

Isoform- and cell cycle-dependent substrate degradation by the Fbw7 ubiquitin ligase.

J. E. Grim, M. P. Gustafson, R. K. Hirata, A. C. Hagar, J. Swanger, M. Welcker, H. C. Hwang, J. Ericsson, D. W. Russell, and B. E. Clurman (2008)
J. Cell Biol. 181, 913-920
 |  Abstract »  |  Full Text »  |  PDF »

The molecular logic of Notch signaling - a structural and biochemical perspective.

W. R. Gordon, K. L. Arnett, and S. C. Blacklow (2008)
J. Cell Sci. 121, 3109-3119
 |  Abstract »  |  Full Text »  |  PDF »

Proteasomal Regulation of the Proliferation vs. Meiotic Entry Decision in the Caenorhabditis elegans Germ Line.

L. D. MacDonald, A. Knox, and D. Hansen (2008)
Genetics 180, 905-920
 |  Abstract »  |  Full Text »  |  PDF »

Zfp64 participates in Notch signaling and regulates differentiation in mesenchymal cells.

K. Sakamoto, Y. Tamamura, K.-i. Katsube, and A. Yamaguchi (2008)
J. Cell Sci. 121, 1613-1623
 |  Abstract »  |  Full Text »  |  PDF »

Downregulation by lipopolysaccharide of Notch signaling, via nitric oxide.

M.-Y. Kim, J.-H. Park, J.-S. Mo, E.-J. Ann, S.-O. Han, S.-H. Baek, K.-J. Kim, S.-Y. Im, J.-W. Park, E.-J. Choi, et al. (2008)
J. Cell Sci. 121, 1466-1476
 |  Abstract »  |  Full Text »  |  PDF »

SCFCdc4 acts antagonistically to the PGC-1{alpha} transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis.

B. L. Olson, M. B. Hock, S. Ekholm-Reed, J. A. Wohlschlegel, K. K. Dev, A. Kralli, and S. I. Reed (2008)
Genes & Dev. 22, 252-264
 |  Abstract »  |  Full Text »  |  PDF »

Notch-1 Mutations Are Secondary Events in Some Patients with T-Cell Acute Lymphoblastic Leukemia.

M. R. Mansour, V. Duke, L. Foroni, B. Patel, C. G. Allen, P. J. Ancliff, R. E. Gale, and D. C. Linch (2007)
Clin. Cancer Res. 13, 6964-6969
 |  Abstract »  |  Full Text »  |  PDF »

Kaposi's sarcoma herpesvirus-encoded latency-associated nuclear antigen stabilizes intracellular activated Notch by targeting the Sel10 protein.

K. Lan, S. C. Verma, M. Murakami, B. Bajaj, R. Kaul, and E. S. Robertson (2007)
PNAS 104, 16287-16292
 |  Abstract »  |  Full Text »  |  PDF »

Notch3 and IL-1beta exert opposing effects on a vascular smooth muscle cell inflammatory pathway in which NF-{kappa}B drives crosstalk.

N. Clement, M. Gueguen, M. Glorian, R. Blaise, M. Andreani, C. Brou, P. Bausero, and I. Limon (2007)
J. Cell Sci. 120, 3352-3361
 |  Abstract »  |  Full Text »  |  PDF »

The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia.

B. J. Thompson, S. Buonamici, M. L. Sulis, T. Palomero, T. Vilimas, G. Basso, A. Ferrando, and I. Aifantis (2007)
J. Exp. Med. 204, 1825-1835
 |  Abstract »  |  Full Text »  |  PDF »

FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to {gamma}-secretase inhibitors.

J. O'Neil, J. Grim, P. Strack, S. Rao, D. Tibbitts, C. Winter, J. Hardwick, M. Welcker, J. P. Meijerink, R. Pieters, et al. (2007)
J. Exp. Med. 204, 1813-1824
 |  Abstract »  |  Full Text »  |  PDF »

Integrin-Linked Kinase Controls Notch1 Signaling by Down-Regulation of Protein Stability through Fbw7 Ubiquitin Ligase.

J.-S. Mo, M.-Y. Kim, S.-O. Han, I.-S. Kim, E.-J. Ann, K. S. Lee, M.-S. Seo, J.-Y. Kim, S.-C. Lee, J.-W. Park, et al. (2007)
Mol. Cell. Biol. 27, 5565-5574
 |  Abstract »  |  Full Text »  |  PDF »

Notch activation stimulates transient and selective binding of Su(H)/CSL to target enhancers.

A. Krejci and S. Bray (2007)
Genes & Dev. 21, 1322-1327
 |  Abstract »  |  Full Text »  |  PDF »

Fbw7 Isoform Interaction Contributes to Cyclin E Proteolysis.

W. Zhang and D. M. Koepp (2006)
Mol. Cancer Res. 4, 935-943
 |  Abstract »  |  Full Text »  |  PDF »

Deletion of presenilin 1 hydrophilic loop sequence leads to impaired gamma-secretase activity and exacerbated amyloid pathology..

Y. Deng, L. Tarassishin, V. Kallhoff, E. Peethumnongsin, L. Wu, Y.-M. Li, and H. Zheng (2006)
J. Neurosci. 26, 3845-3854
 |  Abstract »  |  Full Text »  |  PDF »

Notch Signaling.

L. Miele (2006)
Clin. Cancer Res. 12, 1074-1079
 |  Full Text »  |  PDF »

A molecular link A molecular link between Hairless and Pros26.4, a member of the AAA-ATPase subunits of the proteasome 19S regulatory particle in Drosophila.

D. Muller, A. C. Nagel, D. Maier, and A. Preiss (2006)
J. Cell Sci. 119, 250-258
 |  Abstract »  |  Full Text »  |  PDF »

The interplay between DSL proteins and ubiquitin ligases in Notch signaling.

C. Pitsouli and C. Delidakis (2005)
Development 132, 4041-4050
 |  Abstract »  |  Full Text »  |  PDF »

Control of Genomic Instability and Epithelial Tumor Development by the p53-Fbxw7/Cdc4 Pathway.

J. Perez-Losada, J.-H. Mao, and A. Balmain (2005)
Cancer Res. 65, 6488-6492
 |  Abstract »  |  Full Text »  |  PDF »

Ras activity regulates cyclin E degradation by the Fbw7 pathway.

A. C. Minella, M. Welcker, and B. E. Clurman (2005)
PNAS 102, 9649-9654
 |  Abstract »  |  Full Text »  |  PDF »

The ubiquitin ligase Drosophila Mind bomb promotes Notch signaling by regulating the localization and activity of Serrate and Delta.

E. C. Lai, F. Roegiers, X. Qin, Y. N. Jan, and G. M. Rubin (2005)
Development 132, 2319-2332
 |  Abstract »  |  Full Text »  |  PDF »

Ubiquitin Chains in the Ladder of MAPK Signaling.

A. Laine and Z. Ronai (2005)
Sci. STKE 2005, re5
 |  Abstract »  |  Full Text »  |  PDF »

Deregulation of Cyclin E in Cancer.

S. I. Reed (2005)
Am. Assoc. Cancer Res. Educ. Book 2005, 53-56
 |  Full Text »  |  PDF »

The SV40 Large T Antigen Contains a Decoy Phosphodegron That Mediates Its Interactions with Fbw7/hCdc4.

M. Welcker and B. E. Clurman (2005)
J. Biol. Chem. 280, 7654-7658
 |  Abstract »  |  Full Text »  |  PDF »

Normal Immune System Development in Mice Lacking the Deltex-1 RING Finger Domain.

S. Storck, F. Delbos, N. Stadler, C. Thirion-Delalande, F. Bernex, C. Verthuy, P. Ferrier, J.-C. Weill, and C.-A. Reynaud (2005)
Mol. Cell. Biol. 25, 1437-1445
 |  Abstract »  |  Full Text »  |  PDF »

Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia.

A. P. Weng, A. A. Ferrando, W. Lee, J. P. Morris IV, L. B. Silverman, C. Sanchez-Irizarry, S. C. Blacklow, A. T. Look, and J. C. Aster (2004)
Science 306, 269-271
 |  Abstract »  |  Full Text »  |  PDF »

The Caenorhabditis elegans F-box protein SEL-10 promotes female development and may target FEM-1 and FEM-3 for degradation by the proteasome.

S. Jager, H. T. Schwartz, H. R. Horvitz, and B. Conradt (2004)
PNAS 101, 12549-12554
 |  Abstract »  |  Full Text »  |  PDF »

Monoubiquitination and endocytosis direct {gamma}-secretase cleavage of activated Notch receptor.

N. Gupta-Rossi, E. Six, O. LeBail, F. Logeat, P. Chastagner, A. Olry, A. Israel, and C. Brou (2004)
J. Cell Biol. 166, 73-83
 |  Abstract »  |  Full Text »  |  PDF »

Involvement of Notch signaling in hippocampal synaptic plasticity.

Y. Wang, S. L. Chan, L. Miele, P. J. Yao, J. Mackes, D. K. Ingram, M. P. Mattson, and K. Furukawa (2004)
PNAS 101, 9458-9462
 |  Abstract »  |  Full Text »  |  PDF »

Evidence That C Promoter-binding Factor 1 Binding Is Required for Notch-1-mediated Repression of Activator Protein-1.

J. Chu and E. H. Bresnick (2004)
J. Biol. Chem. 279, 12337-12345
 |  Abstract »  |  Full Text »  |  PDF »

Defective cardiovascular development and elevated cyclin E and Notch proteins in mice lacking the Fbw7 F-box protein.

M. T. Tetzlaff, W. Yu, M. Li, P. Zhang, M. Finegold, K. Mahon, J. W. Harper, R. J. Schwartz, and S. J. Elledge (2004)
PNAS 101, 3338-3345
 |  Abstract »  |  Full Text »  |  PDF »

Mouse Fbw7/Sel-10/Cdc4 Is Required for Notch Degradation during Vascular Development.

R. Tsunematsu, K. Nakayama, Y. Oike, M. Nishiyama, N. Ishida, S. Hatakeyama, Y. Bessho, R. Kageyama, T. Suda, and K. I. Nakayama (2004)
J. Biol. Chem. 279, 9417-9423
 |  Abstract »  |  Full Text »  |  PDF »

The Ubiquitin Ligase SCFFbw7 Antagonizes Apoptotic JNK Signaling.

A. S. Nateri, L. Riera-Sans, C. D. Costa, and A. Behrens (2004)
Science 303, 1374-1378
 |  Abstract »  |  Full Text »  |  PDF »

Association of Transcription Factor YY1 with the High Molecular Weight Notch Complex Suppresses the Transactivation Activity of Notch.

T.-S. Yeh, Y.-M. Lin, R.-H. Hsieh, and M.-J. Tseng (2003)
J. Biol. Chem. 278, 41963-41969
 |  Abstract »  |  Full Text »  |  PDF »

Phosphorylation by Glycogen Synthase Kinase-3{beta} Down-regulates Notch Activity, a Link for Notch and Wnt Pathways.

L. Espinosa, J. Ingles-Esteve, C. Aguilera, and A. Bigas (2003)
J. Biol. Chem. 278, 32227-32235
 |  Abstract »  |  Full Text »  |  PDF »

Mammalian Numb Proteins Promote Notch1 Receptor Ubiquitination and Degradation of the Notch1 Intracellular Domain.

M. A. McGill and C. J. McGlade (2003)
J. Biol. Chem. 278, 23196-23203
 |  Abstract »  |  Full Text »  |  PDF »

Two suppressors of sel-12 encode C2H2 zinc-finger proteins that regulate presenilin transcription in Caenorhabditis elegans.

B. Lakowski, S. Eimer, C. Gobel, A. Bottcher, B. Wagler, and R. Baumeister (2003)
Development 130, 2117-2128
 |  Abstract »  |  Full Text »  |  PDF »

hephaestus encodes a polypyrimidine tract binding protein that regulates Notch signalling during wing development in Drosophila melanogaster.

D. A. Dansereau, M. D. Lunke, A. Finkielsztein, M. A. Russell, and W. J. Brook (2003)
Development 129, 5553-5566
 |  Abstract »  |  Full Text »  |  PDF »

Genetic Analysis of Caenorhabditis elegans glp-1 Mutants Suggests Receptor Interaction or Competition.

A. S.-R. Pepper, D. J. Killian, and E. J. A. Hubbard (2003)
Genetics 163, 115-132
 |  Abstract »  |  Full Text »  |  PDF »

Presenilin-dependent Intramembrane Proteolysis of CD44 Leads to the Liberation of Its Intracellular Domain and the Secretion of an Abeta -like Peptide.

S. Lammich, M. Okochi, M. Takeda, C. Kaether, A. Capell, A.-K. Zimmer, D. Edbauer, J. Walter, H. Steiner, and C. Haass (2002)
J. Biol. Chem. 277, 44754-44759
 |  Abstract »  |  Full Text »  |  PDF »

The Notch Ligand Jagged-1 Is Able to Induce Maturation of Monocyte-Derived Human Dendritic Cells.

S. Weijzen, M. P. Velders, A. G. Elmishad, P. E. Bacon, J. R. Panella, B. J. Nickoloff, L. Miele, and W. M. Kast (2002)
J. Immunol. 169, 4273-4278
 |  Abstract »  |  Full Text »  |  PDF »

hCDC4 Gene Mutations in Endometrial Cancer.

C. H. Spruck, H. Strohmaier, O. Sangfelt, H. M. Muller, M. Hubalek, E. Muller-Holzner, C. Marth, M. Widschwendter, and S. I. Reed (2002)
Cancer Res. 62, 4535-4539
 |  Abstract »  |  Full Text »  |  PDF »

Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex.

C. J. Fryer, E. Lamar, I. Turbachova, C. Kintner, and K. A. Jones (2002)
Genes & Dev. 16, 1397-1411
 |  Abstract »  |  Full Text »  |  PDF »

Insulin-degrading Enzyme Rapidly Removes the beta -Amyloid Precursor Protein Intracellular Domain (AICD).

D. Edbauer, M. Willem, S. Lammich, H. Steiner, and C. Haass (2002)
J. Biol. Chem. 277, 13389-13393
 |  Abstract »  |  Full Text »  |  PDF »

Notch: a membrane-bound transcription factor.

R. Kopan (2002)
J. Cell Sci. 115, 1095-1097
 |  Full Text »  |  PDF »

c-Cbl Binding and Ubiquitin-dependent Lysosomal Degradation of Membrane-associated Notch1.

B. M. Jehn, I. Dittert, S. Beyer, K. von der Mark, and W. Bielke (2002)
J. Biol. Chem. 277, 8033-8040
 |  Abstract »  |  Full Text »  |  PDF »