ライフサイエンスコーパス: numb

1 component of the Trop2 proteolytic complex (Numb).

2 ay be a direct or indirect effect of loss of Numb.

3 essed in these cells but is not inhibited by Numb.

4 crucial for MDM2-mediated ubiquitination of NUMB.

5 lso involved in forming the interaction with NUMB.

6 ed to the phospho-tyrosine binding domain of Numb.

7 s regulates the tumor suppressor activity of Numb.

8 activity facilitates ENF induced by phospho-Numb.

9 ein Musashi2 (Msi2), which in turn represses Numb.

10 nd that these phenotypes were independent of Numb.

11 the PTSD symptoms of anhedonia and emotional numbing.

12 nearby HPCs, thus maintaining expression of Numb (a cell fate determinant) within these cells and th

13 ression and a change in splicing isoforms of Numb, a cell-fate determination gene.

14 ignaling, it is not necessarily dependent on numb, a gene classically involved in biasing Notch activ

15 e of attenuating Notch signaling by inducing Numb, a membrane-associated protein that inhibits Notch

16 n to inhibit Notch signaling and up-regulate Numb, a Notch inhibitor.

17 ng the NOTCH pathway through inactivation of NUMB, a NOTCH signaling repressor.

18 Disruption of Numb accelerated and destabilized ADM in the context of

19 s phospho-Numb levels, attenuates endogenous Numb activity and causes ectopic neuroblast formation (E

20 uncover a molecular mechanism that regulates Numb activity and suggest a novel role for Dronc caspase

21 Numb also controls progenitor maturation.

22 r cells, accumulating evidence supports that Numb also has a critical role in adult tissues and cance

23 Thus, Rbfox3-dependent Numb alternative splicing plays an important role in the

24 within the phosphotyrosine binding domain of NUMB (amino acids 113-148) mediates binding to both thes

25 n and quantitation of cell fate determinants Numb and alpha-adaptin by confocal microscopy were used

26 ential inheritance of cell fate determinants Numb and alpha-Adaptin.

27 ction in part by activating EGFR, AP2M1, and NUMB and as the molecular targets underlying the antivir

28 protein 4) and endocytosis adaptor proteins Numb and epidermal growth factor receptor pathway substr

29 otch pathway by suppressing Notch repressors Numb and Fbxw7 via trimethylation of histone H3 at Lys27

30 interacts with multiple proteins, including NUMB and HES1, to form complexes that participate in int

31 titioning of the fate determinants including Numb and induces supernumerary neuroblasts in larval bra

32 f alpha-Ada interacts with the C terminus of Numb and is important for alpha-Ada function in the sens

33 of neuronal differentiation factors such as Numb and Miranda to the basal cortical domain.

34 activation and cellular polarity, including Numb and Myc, which encode two key factors for the speci

35 Our results tie Numb and Notch-signaling through a single player, Neur,

36 Numb family proteins (NFPs), including Numb and numb-like (Numbl), are cell fate determinants f

37 Numb and Numbl act to determine mammary myoepithelial ce

38 Here, we show that Numb and Numbl are enriched in mammary myoepithelial cel

39 Numb and Numbl function via repression of the Notch sign

40 These findings highlight the importance of Numb and Numbl in the control of myoepithelial cell fate

41 Further investigations revealed that NUMB and NUMBL interacted with small GTPase Rab7 to tran

42 ies provide insight into mechanisms by which NUMB and NUMBL promote cardiomyocyte cell cycle withdraw

43 Loss of NUMB and NUMBL resulted in a partial block of late endos

44 y NFP function in later cardiac development, Numb and Numbl were deleted specifically in heart to gen

45 ve found that the endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2

46 n within epicardial cells, and disruption of Numb and Numblike expression in the epicardium led to ra

47 We show here that Numb and p53 are the constituents of a high molecular ma

48 of p53/hypoxia pathway-associated molecules NUMB and PDGFA occurred more frequently in IPF or emphys

49 ng questions about the restricted ability of Numb and Sanpodo to inhibit and to promote, respectively

50 (ie, dysphoria) symptoms, such as emotional numbing and depressive symptoms.

51 This +4 antral SC is Notch1(low)/ Numb(+) and repressed by signaling from gastrin-expressi

52 Dronc caspase as a novel binding partner of Numb, and demonstrate that overexpression of Dronc suppr

53 loping molars showed changes in Runx2, Gli1, Numb, and Notch expression in the dental pulp cells and

54 rward circuit involving DLL4, NOTCH3, MSI-1, NUMB, and NOTCH1 may be relevant for regulation of NOTCH

55 tellite cell proliferation in the absence of Numb, and the proliferation defect was confirmed in sate

56 We use conditional Numb- and Numbl-knockout mouse models to demonstrate tha

57 Our data suggest that Numb antagonises Notch signalling in the neural precurso

58 Together with our finding that Numb antagonizes Notch signaling in late-stage RPCs, and

59 hway and the intrinsic cell-fate determinant Numb appear to regulate asymmetric divisions in flies an

60 sm2) and NuMA, and the cell fate determinant Numb are asymmetrically localized in embryonic lung dist

61 We also show that Neur and Numb are interdependent for their asymmetric-localizatio

62 Herein, we identified Numb as a novel substrate of Polo-like kinase 1 (Plk1).

63 In addition, the data identify Numb as a novel target gene of the Wnt signaling pathway

64 lling to act for one victim, we often become numb as the number of victims increases.

65 mass spectrometry, we identify TBC1D15 as a Numb-associated protein and demonstrate that its amino-t

66 motes both perpendicular division as well as Numb asymmetric segregation to one daughter in mitotic d

67 In the absence of Numb, asymmetric terminal divisions that generate a phot

68 istle development, precursor cells segregate Numb asymmetrically to one of their progeny cells, rende

69 otyrosine-binding domain and is critical for Numb binding in vitro.

70 stimulated with the chemotactic factor BDNF, Numb binds to activated TrkB, the BDNF receptor, and fun

71 Numb blocks N-signaling in one of the two daughters of a

72 cells carrying the unphosphorylated form of Numb by Plk1 are more sensitive to doxorubicin, a classi

73 Numb can antagonize Notch signaling to diversify the fat

74 was also inversely correlated with avoidance/numbing CAPS symptoms.

75 eatitis or pancreatic injury, elimination of Numb causes dedifferentiated acinar cells to undergo apo

76 NA targets have been characterized so far: m-numb, CDKN1A, and c-mos.

77 e number of CD44(+), bromodeoxyuridine+, and NUMB(+) cells, indicating an increase in symmetric divis

78 suicide attempters exhibit an 'interoceptive numbing' characterized by increased tolerance for aversi

79 Our data therefore suggest that Numb controls the balance between Notch receptor recycli

80 e serine/threonine polo-like kinase Plk1 and Numb cycles in a cell-cycle-dependent fashion along with

81 Quantitative RT-PCR from Numb-deficient satellite cells demonstrated highly up-re

82 ic siRNA rescued the proliferation defect of Numb-deficient satellite cells.

83 at Spdo is sorted toward late endosomes in a Numb-dependent manner.

84 rily conserved motif that has been linked to Numb-dependent regulation in vertebrates and further sup

85 analysis of Sanpodo NPAF mutants shows that Numb-dependent Sanpodo endocytic targeting can be uncoup

86 However, the significance of Numb-dependent Sanpodo regulation is unclear.

87 asma membrane to intracellular vesicles in a Numb-dependent way after neural progenitor cell mitosis.

88 e, and hyperarousal) and loss (ie, emotional numbing, depression/dysphoria, generalized anxiety) symp

89 Strong connectivity among emotional numbing, detachment from others, and disinterest in acti

90 By binding to both domains on MDM2, NUMB disrupts the MDM2-p53 complex and MDM2-catalyzed ub

91 mmetrically localizes in a late GMC-1 to the Numb domain and Neur mediates asymmetric division via tw

92 Neur also enhances Notch since in neur; numb double mutants, both sibling cells often adopt a mi

93 as opposed to an RP2 fate observed in Notch; numb double mutants.

94 , is targeted for proteasomal degradation by Numb during differentiation.

95 r, our findings present a novel function for Numb during symmetric cell division.

96 These data indicate a unique function for Numb during the initial activation and proliferation of

97 interference-mediated depletion of AP2M1 or NUMB, each a substrate of AAK1 and/or GAK, or overexpres

98 itosis of purified mammary stem cells (SCs), Numb ensures the asymmetric outcome of self-renewing div

99 When phosphorylated, Numb exhibits increased efficacy in binding TrkB and in

100 aptors and coat proteins, such as AP-4, ARH, Numb, exomer, and retromer, have also been implicated.

101 nown interaction with the intronic 3 site of NUMB exon 9 contributing to regulation of the Notch path

102 Notably, loss of Msi2 restores Numb expression and significantly impairs the developmen

103 we investigated the effects of nandrolone on Numb expression and Wnt signaling and determined the rol

104 Up-regulation of Numb expression by nandrolone was blocked by the Wnt inh

105 tudy, we report that a targeted knockdown of Numb expression causes a G(2)-M arrest and reduced cell

106 roles of Wnt signaling in nandrolone-induced Numb expression in C2C12 myoblasts.

107 itionally requires Wingless, which regulates Numb expression in the AMP lineage.

108 Liver-specific TBC1D15 deficiency or non-p-NUMB expression reduced TIC numbers and HCC development.

109 Reduction in Numb expression resulted in mislocalization of Plk1 at b

110 We suggest that dysregulation of Numb expression results in mislocalized Plk1 and poor ce

111 ing, and manipulations of Notch signaling or Numb expression suppress mPar3 regulation of radial glia

112 Interestingly, Numb expression was required for Plk1 protein stability

113 he chronic phase is marked by high levels of Numb expression whereas the blast crisis phase has low l

114 activation activity and leading to decreased NUMB expression, and further activates the downstream NO

115 eas the blast crisis phase has low levels of Numb expression, and that ectopic expression of Numb pro

116 enced by c-kit(+), NKX2-5(+), NOTCH1(+), and NUMB(+) expression.

117 text of oncogenic Kras (in p48Cre;Kras(G12D);Numb(f/f) and p48Cre(ER);Kras(G12D);Numb(f/f) mice).

118 -function alleles of Numb (p48Cre/p48Cre(ER);Numb(f/f) and p48Cre/p48Cre(ER);Kras(G12D);Numb(f/f) mic

119 );Numb(f/f) and p48Cre/p48Cre(ER);Kras(G12D);Numb(f/f) mice) to study the roles of Numb in pancreatic

120 as(G12D);Numb(f/f) and p48Cre(ER);Kras(G12D);Numb(f/f) mice).

121 Numb family proteins (NFPs), including Numb and numb-lik

122 This interaction prevents Numb from binding Notch1, rescuing it from Numb-mediated

123 translational modifications of Numb uncouple Numb from p53 and lead to p53 destabilization.

124 molecular and cellular mechanisms underlying Numb function in a stem cell setting remain poorly defin

125 we analyse the role of Notch signalling and numb function in the development of the mechanosensory o

126 Therefore, Numb functions in a feed-forward loop to promote chemota

127 Numb functions in progenitor cell fate determination and

128 imaging in retinal explants, we show that a Numb fusion protein is asymmetrically inherited by the d

129 responsive microRNA, miR-146a, that targeted NUMB gene and alleviated the suppression of SHH signalin

130 e observed that the proximal promoter of the Numb gene had functional Tcf binding elements to which b

131 ch pathway targets, the second intron of the numb gene was found to contain a statistically significa

132 nuclear Trop2 ICD and cyclin D1, and reduced Numb, had reduced recurrence-free survival probability (

133 The ACBD3 binding region of Numb harbors two aPKC phosphorylation sites, serines 48

134 The adaptor protein Numb has been implicated in the switch between cell prol

135 By contrast, protein numb homolog (NUMB) is present only in the subset of the

136 2-mediated ubiquitination and degradation of NUMB impacting on the stabilization of p53 in cells.

137 t cell fate determinant and tumor suppressor Numb imposes asymmetric cell divisions in mammary stem c

138 by promoting the asymmetric localization of Numb in a GMC-1 via down-regulation of the transcription

139 re, we show that miR-34a directly suppresses Numb in early-stage colon cancer stem cells (CCSCs), for

140 hat forced expression of the Notch inhibitor NUMB in HepaRG resulted in enhanced hepatocyte different

141 n is essential for asymmetric segregation of Numb in mitotic neuroblasts and suppression of the super

142 rectly impinged on asymmetric segregation of Numb in mitotic neuroblasts, both the phosphomimetic and

143 Polarization of Numb in mitotic phospho-histone positive cells demonstra

144 trically segregate the cell fate determinant Numb in order to block Notch signaling in only one of th

145 the inclusion/exclusion of exons 3 and 9 of Numb in P19 cells.

146 (G12D);Numb(f/f) mice) to study the roles of Numb in pancreatic regeneration and ADM.

147 generation, indicating an essential role for Numb in photoreceptor cell biology.

148 Interestingly, we report that loss of Numb in photoreceptors does not affect the localization

149 Furthermore, overexpression of Numb in satellite cells inhibited Myostatin expression.

150 t a model in which asymmetric inheritance of Numb in sister cells of terminal divisions might create

151 amplifying Notch signaling in the absence of Numb in the 'A' daughter cell and inhibiting Notch signa

152 nhibiting Notch signaling in the presence of Numb in the 'B' daughter cell.

153 ible explanation for the decreased levels of Numb in the blast crisis phase, we show that NUP98-HOXA9

154 dy the role of the endocytic adaptor protein Numb in the developing mouse retina.

155 mitotic neuroblasts reduces the function of Numb in the future progenitor cells.

156 ate a junctional complex of beta-catenin and Numb in the regulation of spindle orientation.

157 Rod photoreceptor-specific inactivation of numb in vivo leads to progressive photoreceptor degenera

158 Recent work now demonstrates in vivo that Numb inactivates Notch by promoting its endocytosis.

159 Using clonal numb inactivation in retinal progenitor cells (RPCs), we

160 Further studies showed that Numb inhibits Notch1 signaling by promoting the degradat

161 phila melanogaster sensory bristle lineages, Numb inhibits the recycling of Notch and its trafficking

162 Cell-fate-determinant molecule NUMB-interacting protein (TBC1D15) is overexpressed and

163 ogether, our results indicate that Notch and Numb interaction may influence the sensitivity of neuron

164 yeast-two hybrid system we isolated a novel Numb interactor in zebrafish called NBP which is an orth

165 Mechanistically, we show that Numb interacts with both subunits of the Cng channel and

166 ation and colocalization studies showed that Numb interacts with the serine/threonine polo-like kinas

167 part by ensuring asymmetric partitioning of Numb into the future progenitor cell where Numb maintain

168 atic event and is characterized by avoidance/numbing, intrusive symptoms and flashbacks, mood and cog

169 In the human mammary gland, Numb is a tumor suppressor and regulates p53 levels.

170 Interestingly, Numb is also a substrate of aPKC.

171 Numb is an adaptor protein implicated in diverse basic c

172 Numb is an important regulator of acinar cell differenti

173 Numb is an intrinsic regulator of the Notch pathway and

174 Numb is asymmetrically localized in a GMC and is segrega

175 We found that NUMB is asymmetrically localized in CE cells, suggesting

176 These results indicate that NUMB is necessary for establishing polarity in CE cells,

177 Furthermore, Numb is needed in the lateral but not adPN or vPN lineag

178 At late stages, however, Numb is no longer required for cell-cycle progression, b

179 utants the GMC-1 identity is not altered but Numb is non-asymmetrically localized due to an up-regula

180 Whereas Numb is polarized by direct aPKC phosphorylation, Mirand

181 etinal progenitor cells (RPCs), we show that Numb is required for normal cell-cycle progression at ea

182 perpendicular division is not maintained and Numb is segregated to both daughter cells in mitotic epi

183 lopmental Cell, Zhou et al. demonstrate that Numb is the focal point in mediating the chemotactic res

184 Although Numb is well-recognized as a cell-fate determinant in st

185 By contrast, protein numb homolog (NUMB) is present only in the subset of the tumors that a

186 ch reduction was reversed by an RBM4-induced Numb isoform containing exon 3 but lacking exon 9.

187 ional relevance of the TFW-induced switch in Numb isoforms is not known.

188 PC12 cells stably overexpressing Numb isoforms lacking the PTB insertion exhibited higher

189 vide evidence that the TFW-induced switch in Numb isoforms regulates Notch signaling strength and Not

190 PC6) when compared with those overexpressing Numb isoforms with the PTB insertion.

191 effects caused by the TFW-induced switch in Numb isoforms.

192 were rescued by RBM4-induced exon 9-lacking Numb isoforms.

193 disintegrated upon activation of aPKCzeta, a Numb kinase.

194 The mammary gland of Numb-knockout mice displays an expansion of the SC compa

195 showed that Plk1-mediated phosphorylation of Numb leads to its enhanced proteasomal degradation and i

196 evels and can be inhibited by restoration of Numb levels or p53 activity, which results in successful

197 or genetic manipulation that boosts phospho-Numb levels, attenuates endogenous Numb activity and cau

198 y, Tak1 deficiency correlated with increased NUMB-like (NUMBL) levels.

199 We have reported recently that NUMB-like (NUMBL) protein modulates osteoclastogenesis b

200 b family proteins (NFPs), including Numb and numb-like (Numbl), are cell fate determinants for multip

201 Loss of adherens junctions also disrupted Numb localization within epicardial cells, and disruptio

202 port here that the endocytic adaptor protein Numb localizes to the inner, but not the outer segment o

203 Furthermore, we observed that Numb looses its characteristic membrane localization in

204 At this level, Numb loss associates with the epithelial-to-mesenchymal

205 f Numb into the future progenitor cell where Numb maintains restricted potential independently of reg

206 perarousal symptoms) and loss (ie, emotional numbing, major depressive disorder, and generalized anxi

207 In addition, Notch/Numb-mediated binary sibling fates underlie the producti

208 wn in kidney epithelial cells cause p21- and Numb-mediated cell cycle arrest.

209 s Numb from binding Notch1, rescuing it from Numb-mediated lysosomal degradation.

210 Therefore, dysregulation of NUMB-mediated suppression of NOTCH1 by TNFalpha/IKKalpha

211 the interaction between Notch signalling and Numb might play a similar role in both systems.

212 Similar NBP and Numb morphant phenotype such as impaired convergence and

213 ors, sFRP1 and DKK1, whereas Wnt3a increased Numb mRNA and protein expression.

214 Nandrolone increased Numb mRNA and protein levels and T cell factor (Tcf) tra

215 activities are due to miR-146a targeting the NUMB mRNA, a repressor of Notch signaling.

216 opulation and that excess Notch signaling in numb mutants requires the recycling endosome GTPase Rab1

217 ciency or expression of non-phosphorylatable NUMB mutations.

218 deletion of the ancient cell-fate regulator Numb (Nb) and its homologue Numblike (Nbl) depletes CPCs

219 sion of the endogenous inhibitor of Notch-1, numb (Nb), this can be prevented by AEA and 2-arachidono

220 In Drosophila neural stem cells (NSCs), Numb/Notch (N) signaling plays a key role in this proces

221 is an inhibitor of the IkappaB kinase alpha/NUMB/NOTCH pathway and an inducer of hepatocytic differe

222 enotype and mediated by IkappaB kinase alpha/NUMB/NOTCH signaling.

223 Here, we report a TNFalpha/IKKalpha/FOXA2/NUMB/NOTCH1 pathway that is critical for inflammation-me

224 rced expression of a phospho-mimetic form of Numb (Numb-TS4D) or genetic manipulation that boosts pho

225 out mouse models to demonstrate that loss of Numb/Numbl compromised the myoepithelial layer and expan

226 the spider numb RNAi phenotype resembles the numb/numblike loss of function phenotypes in the mammali

227 st this hypothesis, we conditionally deleted Numb on a Numbl mutant background just prior to gonadoge

228 Null mutants of numb or the alpha-subunit of Adaptor Protein complex-2 e

229 Loss of BRCA1, NUMB, or HES1 or chemically induced ICL damage in primar

230 The cell fate determinant Numb orchestrates tissue morphogenesis and patterning in

231 ell as mice with loss-of-function alleles of Numb (p48Cre/p48Cre(ER);Numb(f/f) and p48Cre/p48Cre(ER);

232 is known about the biological control of the Numb-p53 interaction.

233 nhanced proteasomal degradation and impaired Numb/p53 pathway, thus providing another mechanism how P

234 Opioids such as morphine numb pain but often concomitantly induce itch.

235 These data show that the Musashi-Numb pathway can control the differentiation of CML cell

236 ng the efficacy of chemotherapy by targeting Numb phosphorylation by Plk1.

237 GAK, or overexpression of either an AP2M1 or NUMB phosphorylation site mutant inhibited HCV entry.

238 F motif is predicted to bind directly to the Numb phosphotyrosine-binding domain and is critical for

239 -sensing cilia, raising the possibility that Numb plays a part in the regulation of protein trafficki

240 ulation of Sanpodo at the plasma membrane in Numb-positive cells in vivo.

241 se brain also exhibited aberrant splicing of Numb pre-mRNA.

242 Numb premRNA encoding a signaling adaptor protein was fo

243 unction with its interacting partner protein Numb, preserves this asymmetry and functions as a vital

244 These results suggest a model in which Numb prevents targeting of Cng channels to the inner seg

245 , we show that the endocytic adaptor protein Numb, previously characterized for its role in cell prol

246 indicated that the Tcf binding sites in the Numb promoter are required for the nandrolone-induced Nu

247 Thus, Numb promotes BDNF-dependent aPKC activation.

248 b expression, and that ectopic expression of Numb promotes differentiation and impairs advanced-phase

249 Drosophila Numb protein regulates this process through its preferen

250 cells with anti-NOTCH2/3 antibody increased NUMB protein while significantly reducing formation of t

251 integrated with the autonomous action of the Numb protein, a Notch pathway antagonist.

252 ion of the gene is regulated by the Notch to Numb ratio within the sensory precursors.

253 Numb regulated cardiac progenitor cell differentiation i

254 Numb regulates cell junctions, integrins, and the activi

255 We find that the endosomal adaptor protein Numb regulates levels of Notch receptor trafficking to R

256 ontrast, the canonical cell-fate determinant Numb regulates Notch levels in a continuously graded man

257 rtebrates and further support the model that Numb regulates Notch signaling independently of Sanpodo

258 behavior and reveal a new mechanism by which Numb regulates NSC behavior through N.

259 In lgl mutant brains, Numb remained localized in the cortex of mitotic neurobl

260 mation of excess neuroblasts by inactivating Numb remains controversial.

261 How Numb restricts the proliferation and self-renewal potent

262 t of the third larval instar, the removal of Numb resulted in all neurons assuming the A fate.

263 Loss of Numb resulted in premature dedifferentiation of acinar c

264 Interestingly, the spider numb RNAi phenotype resembles the numb/numblike loss of

265 la sensory organ precursor cell development, Numb segregates asymmetrically and functions as a cell f

266 These lineage-specific outputs of Notch/Numb signaling show that a universal mechanism of binary

267 ease progression is regulated by the Musashi-Numb signalling axis.

268 e through the endocytic system, we show that Numb specifically suppresses a recycled Notch receptor s

269 Depleting a specific Numb splice isoform reproduced similar neuronal differen

270 Forced expression of the relevant Numb splice isoform was sufficient to rescue, in an isof

271 siological relevance of the existence of the Numb splice variants and their exact regulation are stil

272 phomimetic and non-phosphorylatable forms of Numb suppressed formation of excess neuroblasts triggere

273 We previously reported that Numb switches from isoforms containing the insertion in

274 Numb thereby restricts mammary stem cell expansion and c

275 f the endocytic AP-2 complex, interacts with Numb through a new mode of interaction to regulate NSC h

276 NBP interacts with the PTB domain of Numb through a region well conserved among vertebrate Ka

277 ing, and NSC homeostasis by interacting with Numb through new domains in both proteins previously not

278 The need for Numb to direct Notch signaling correlated with a decreas

279 dicate that RBM4 modulates exon selection of Numb to generate isoforms that promote neuronal cell dif

280 ions temporally after Brain tumor (Brat) and Numb to restrict the developmental potential of uncommit

281 ells that do not inherit Numb, yet must make Numb to segregate to one daughter during their own divis

282 esponsive cis-regulatory module that directs numb transcription in the pIIa and pIIIb cells of the br

283 ecular mechanism underlying up-regulation of Numb transcription with a critical role for increased ca

284 oter are required for the nandrolone-induced Numb transcriptional activation in this cell line.

285 ts amino-terminal domain disengages p53 from Numb, triggering p53 proteolysis and promoting self-rene

286 xpression of Dronc suppresses the effects of Numb-TS4D in a non-apoptotic and possibly non-catalytic

287 xpression of a phospho-mimetic form of Numb (Numb-TS4D) or genetic manipulation that boosts phospho-N

288 ion that post-translational modifications of Numb uncouple Numb from p53 and lead to p53 destabilizat

289 Therefore, we have identified the mechanism NUMB uses to regulate the steady-state levels of the p53

290 Numb was found to regulate multiple signaling pathways i

291 When Numb was removed at the start of larval neurogenesis, bo

292 Using two genetic approaches to ablate Numb, we determined that, in its absence, muscle regener

293 tion, we show that the cell fate determinant Numb, which depletes CML stem cells, is increased in the

294 ergo asymmetric cell division by segregating Numb, which inhibits Notch signaling, into the pIIb daug

295 spindle orientation and the localization of Numb, which inhibits Notch signaling.

296 triggered by the endogenous Notch inhibitor Numb, which is upregulated in the stem cells by Wnt7a de

297 Thus, both its daughters inherit Numb, which prevents Notch from specifying a sib identit

298 the translation of its target mRNAs, p21 and Numb, whose protein levels are markedly increased in kid

299 chanism to bind to the cell fate determinant NUMB with both the N-terminal hydrophobic pocket and the

300 the two precursor cells that do not inherit Numb, yet must make Numb to segregate to one daughter du