ライフサイエンスコーパス: numb

1 component of the Trop2 proteolytic complex (Numb).

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

3 crucial for MDM2-mediated ubiquitination of NUMB.

4 lso involved in forming the interaction with NUMB.

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

6 s regulates the tumor suppressor activity of Numb.

7 activity facilitates ENF induced by phospho-Numb.

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

9 ay be a direct or indirect effect of loss of 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 titioning of the fate determinants including Numb and induces supernumerary neuroblasts in larval bra

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

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

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

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

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

36 Numb and Numbl act to determine mammary myoepithelial ce

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

38 Numb and Numbl function via repression of the Notch sign

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

54 with PTSD--intrusive memories, avoidance and numbing, and hyperarousal--avoidance and numbing appear

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

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

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

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

59 and numbing, and hyperarousal--avoidance and numbing appear to be the most specific for identificatio

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 of the Wnt and Notch pathways, and position Numb as a key mediator of this process.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

109 Interestingly, Numb expression was required for Plk1 protein stability

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

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

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

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

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

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

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

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

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

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

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

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

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

123 ious work in other model systems showed that Numb functions as a Notch signaling pathway antagonist,

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

125 Numb functions in progenitor cell fate determination and

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

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

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

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

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

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

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

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

134 2-mediated ubiquitination and degradation of NUMB impacting on the stabilization of p53 in cells.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

154 o be mediated by the transient expression of Numb in the hemangioblast-derived blast cell colonies.

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

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

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

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

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

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

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

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

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

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

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

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

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

168 Interestingly, Numb is also a substrate of aPKC.

169 Numb is an adaptor protein implicated in diverse basic c

170 Numb is an important regulator of acinar cell differenti

171 Numb is an intrinsic regulator of the Notch pathway and

172 Numb is asymmetrically localized in a GMC and is segrega

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

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

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

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

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

178 Whereas Numb is polarized by direct aPKC phosphorylation, Mirand

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

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

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

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

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

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

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

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

187 e determined the influence of the four human Numb isoforms on the intracellular trafficking and proce

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

189 Neural cells expressing Numb isoforms that lack the insert in the PTB (short PTB

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 nts, we identified a sea urchin homologue of Numb (LvNumb).

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

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

208 s initially established as a result of Notch/Numb-mediated asymmetric divisions.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

241 Numb premRNA encoding a signaling adaptor protein was fo

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

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

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

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

246 Thus, Numb promotes BDNF-dependent aPKC activation.

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

248 Drosophila Numb protein regulates this process through its preferen

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

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

251 gesting that the differential effects of the Numb proteins on APP metabolism is likely to be secondar

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