Invited Mini Review : Phosphorylation-dependent regulation of Notch1 signaling: the fulcrum of Notch1 signaling = Invited Mini Review : Phosphorylation-dependent regulation of Notch1 signaling: the fulcrum of Notch1 signaling

다국어 초록 (Multilingual Abstract)

Notch signaling plays a pivotal role in cell fate determination, cellular development, cellular self-renewal, tumor progression, and has been linked to developmental disorders and carcinogenesis. Notch1 is activated through interactions with the ligands of neighboring cells, and acts as a transcriptional activator in the nucleus. The Notch1 intracellular domain (Notch1-IC) regulates the expression of target genes related to tumor development and progression. The Notch1 protein undergoes modification after translation by posttranslational modification enzymes. Phosphorylation modification is critical for enzymatic activation, complex formation, degradation, and subcellular localization. According to the nuclear cycle, Notch1-IC is degraded by E3 ligase, FBW7 in the nucleus via phosphorylation-dependent degradation. Here, we summarize the Notch signaling pathway, and resolve to understand the role of phosphorylation in the regulation of Notch signaling as well as to understand its relation to cancer. [BMB Reports 2015; 48(8): 431-437]

참고문헌 (Reference)

1 Wallberg AE, "p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitro" Mol Cell Biol 22 : 7812 ~ 7819, 2002

2 Logeat F, "The Notch1 receptor is cleaved constitutively by a furin-like convertase" Proc Natl Acad Sci U S A 95 : 8108 ~ 8112, 1998

3 Borggrefe T, "The Notch signaling pathway: transcriptional regulation at Notch target genes" Cell Mol Life Sci 66 : 1631 ~ 1646, 2009

4 Mungamuri SK, "Survival signaling by Notch1: mammalian target of rapamycin (mTOR)-dependent inhibition of p53" Cancer Res 66 : 4715 ~ 4724, 2006

5 Zhou S, "SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function" Mol Cell Biol 20 : 2400 ~ 2410, 2000

6 Wu G, "SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation" Mol Cell Biol 21 : 7403 ~ 7415, 2001

7 Jafar-Nejad H, "Role of glycans and glycosyltransferases in the regulation of Notch signaling" Glycobiology 20 : 931 ~ 949, 2010

8 Guo S, "Role of Notch and its oncogenic signaling crosstalk in breast cancer" Biochim Biophys Acta 1815 : 197 ~ 213, 2011

9 Holt LJ, "Regulatory modules: Coupling protein stability to phopshoregulation during cell division" FEBS Lett 586 : 2773 ~ 2777, 2012

10 Yun Hye Jin, "Regulation of Notch1/NICD and Hes1 Expressions by GSK-3α/β" Molecules and Cells 27 (1) : 15 ~ 19, 2009

11 Oswald F, "RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence Notch target genes" Mol Cell Biol 25 : 10379 ~ 10390, 2005

12 Erbilgin Y, "Prognostic significance of NOTCH1 and FBXW7 mutations in pediatric T-ALL" Dis Markers 28 : 353 ~ 360, 2010

13 Espinosa L, "Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways" J Biol Chem 278 : 32227 ~ 32235, 2003

14 Bedogni B, "Notch1 is an effector of Akt and hypoxia in melanoma development" J Clin Invest 118 : 3660 ~ 3670, 2008

15 Schroeter EH, "Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain" Nature 393 : 382 ~ 386, 1998

16 Bray SJ, "Notch signalling: a simple pathway becomes complex" Nat Rev Mol Cell Biol 7 : 678 ~ 689, 2006

17 Ranganathan P, "Notch signalling in solid tumours: a little bit of everything but not all the time" Nat Rev Cancer 11 : 338 ~ 351, 2011

18 Andersson ER, "Notch signaling: simplicity in design, versatility in function" Development 138 : 3593 ~ 3612, 2011

19 Artavanis-Tsakonas S, "Notch signaling: cell fate control and signal integration in development" Science 284 : 770 ~ 776, 1999

20 Sahlgren C, "Notch signaling mediates hypoxia-induced tumor cell migration and invasion" Proc Natl Acad Sci U S A 105 : 6392 ~ 6397, 2008

21 Bolos V, "Notch signaling in development and cancer" Endocr Rev 28 : 339 ~ 363, 2007

22 Allenspach EJ, "Notch signaling in cancer" Cancer Biol Ther 1 : 466 ~ 476, 2002

23 Chillakuri CR, "Notch receptor-ligand binding and activation: insights from molecular studies" Semin Cell Dev Biol 23 : 421 ~ 428, 2012

24 Krejci A, "Notch activation stimulates transient and selective binding of Su(H)/CSL to target enhancers" Genes Dev 21 : 1322 ~ 1327, 2007

25 Grabher C, "Notch 1activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia" Nat Rev Cancer 6 : 347 ~ 359, 2006

26 Ishitani T, "Nemo-like kinase suppresses Notch signalling by interfering with formation of the Notch active transcriptional complex" Nat Cell Biol 12 : 278 ~ 285, 2010

27 Min SH, "Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase" Mol Cell 46 : 771 ~ 783, 2012

28 Yatim A, "NOTCH1 nuclear interactome reveals key regulators of its transcriptional activity and oncogenic function" Mol Cell 48 : 445 ~ 458, 2012

29 Oswald F, "NF-kappaB2 is a putative target gene of activated Notch-1via RBP-Jkappa" Mol Cell Biol 18 : 2077 ~ 2088, 1998

30 Palomero T, "Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia" Nat Med 13 : 1203 ~ 1210, 2007

31 Nash P, "Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication" Nature 414 : 514 ~ 521, 2001

32 Itoh M, "Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta" Dev Cell 4 : 67 ~ 82, 2003

33 Minella AC, "Mechanisms of tumor suppression by the SCF(Fbw7)" Cell Cycle 4 : 1356 ~ 1359, 2005

34 McElhinny AS, "Mastermind-like transcriptional co-activators: emerging roles in regulating cross talk among multiple signaling pathways" Oncogene 27 : 5138 ~ 5147, 2008

35 Fryer CJ, "Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover" Mol Cell 16 : 509 ~ 520, 2004

36 Fryer CJ, "Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex" Genes Dev 16 : 1397 ~ 1411, 2002

37 Lai EC, "Keeping a good pathway down: transcriptional repression of Notch pathway target genes by CSL proteins" EMBO Rep 3 : 840 ~ 845, 2002

38 Mo JS, "Integrin-linked kinase controls Notch1 signaling by down-regulation of protein stability through Fbw7 ubiquitin ligase" Mol Cell Biol 27 : 5565 ~ 5574, 2007

39 Zavadil J, "Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition" EMBO J 23 : 1155 ~ 1165, 2004

40 Brou C, "Inhibition of the DNA-binding activity of Drosophila suppressor of hairless and of its human homolog, KBF2/RBP-J kappa, by direct protein-protein interaction with Drosophila hairless" Genes Dev 8 : 2491 ~ 2503, 1994

41 Chiang MY, "Identification of a conserved negative regulatory sequence that influences the leukemogenic activity of NOTCH1" Mol Cell Biol 26 : 6261 ~ 6271, 2006

42 Marignol L, "Hypoxia, notch signalling, and prostate cancer" Nat Rev Urol 10 : 405 ~ 413, 2013

43 Foltz DR, "Hyperphosphorylation and association with RBP of the intracellular domain of Notch1" Biochem Biophys Res Commun 286 : 484 ~ 492, 2001

44 Ranganathan P, "Hierarchical phosphorylation within the ankyrin repeat domain defines a phosphoregulatory loop that regulates Notch transcriptional activity" J Biol Chem 286 : 28844 ~ 28857, 2011

45 Foltz DR, "Glycogen synthase kinase-3beta modulates notch signaling and stability" Curr Biol 12 : 1006 ~ 1011, 2002

46 Welcker M, "FBW7 ubiquitin ligase:a tumour suppressor at the crossroads of cell division, growth and differentiation" Nat Rev Cancer 8 : 83 ~ 93, 2008

47 O'Neil J, "FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors" J Exp Med 204 : 1813 ~ 1824, 2007

48 Kong D, "Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells" PLoS One 5 : e12445 ~, 2010

49 Lai EC, "Drosophila neuralized is a ubiquitin ligase that promotes the internalization and degradation of delta" Dev Cell 1 : 783 ~ 794, 2001

50 Song J, "Down-regulation of Notch-dependent transcription by Akt in vitro" FEBS Lett 582 : 1693 ~ 1699, 2008

51 Luo DH, "Differential expression of Notch1 intracellular domain and p21 proteins, and their clinical significance in gastric cancer" Oncol Lett 7 : 471 ~ 478, 2014

52 Espinoza I, "Deadly crosstalk: Notch signaling at the intersection of EMT and cancer stem cells" Cancer Lett 341 : 41 ~ 45, 2013

53 Li N, "Cyclin C is a haploinsufficient tumour suppressor" Nat Cell Biol 16 : 1080 ~ 1091, 2014

54 Fiuza UM, "Cell and molecular biology of Notch" J Endocrinol 194 : 459 ~ 474, 2007

55 Fernandez-Martinez J, "Attenuation of Notch signalling by the Down-syndrome-associated kinase DYRK1A" J Cell Sci 122 : 1574 ~ 1583, 2009

56 Weng AP, "Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia" Science 306 : 269 ~ 271, 2004

57 Ma D, "Aberrant expression and clinical correlation of Notch signaling molecules in breast cancer of Chinese population" Asia Pac J Clin Oncol 7 : 385 ~ 391, 2011

58 Stylianou S, "Aberrant activation of notch signaling in human breast cancer" Cancer Res 66 : 1517 ~ 1525, 2006

59 Mumm JS, "A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1" Mol Cell 5 : 197 ~ 206, 2000

60 Cordle J, "A conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition" Nat Struct Mol Biol 15 : 849 ~ 857, 2008