NUMB

Summary

Gene Symbol: NUMB
Description: NUMB, endocytic adaptor protein
Alias: C14orf41, S171, c14_5527, protein numb homolog, h-Numb, numb homolog
Species: human
Products:     NUMB

Top Publications

  1. Colaluca I, Tosoni D, Nuciforo P, Senic Matuglia F, Galimberti V, Viale G, et al. NUMB controls p53 tumour suppressor activity. Nature. 2008;451:76-80 pubmed publisher
    b>NUMB is a cell fate determinant, which, by asymmetrically partitioning at mitosis, controls cell fate choices by antagonising the activity of the plasma membrane receptor of the NOTCH family...
  2. Di Marcotullio L, Ferretti E, Greco A, De Smaele E, Po A, Sico M, et al. Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination. Nat Cell Biol. 2006;8:1415-23 pubmed
    The developmental protein Numb is a major determinant of binary cell fates...
  3. Pece S, Serresi M, Santolini E, Capra M, Hulleman E, Galimberti V, et al. Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis. J Cell Biol. 2004;167:215-21 pubmed
    The biological antagonism between Notch and Numb controls the proliferative/differentiative balance in development and homeostasis...
  4. McGill M, McGlade C. Mammalian numb proteins promote Notch1 receptor ubiquitination and degradation of the Notch1 intracellular domain. J Biol Chem. 2003;278:23196-203 pubmed
    The cell fate determinant Numb influences developmental decisions by antagonizing the Notch signaling pathway. However, the underlying molecular mechanism of this inhibition is poorly understood...
  5. Wong W, Schumacher C, Salcini A, Romano A, Castagnino P, Pelicci P, et al. A protein-binding domain, EH, identified in the receptor tyrosine kinase substrate Eps15 and conserved in evolution. Proc Natl Acad Sci U S A. 1995;92:9530-4 pubmed
    ..Structural comparison of Eps15 and Eps15r defines a family of signal transducers possessing extensive networking abilities including EH-mediated binding and association with Src homology 3-containing proteins. ..
  6. Santolini E, Puri C, Salcini A, Gagliani M, Pelicci P, Tacchetti C, et al. Numb is an endocytic protein. J Cell Biol. 2000;151:1345-52 pubmed
    b>Numb is a protein that in Drosophila determines cell fate as a result of its asymmetric partitioning at mitosis...
  7. Maiorano E, Favia G, Pece S, Resta L, Maisonneuve P, Di Fiore P, et al. Prognostic implications of NUMB immunoreactivity in salivary gland carcinomas. Int J Immunopathol Pharmacol. 2007;20:779-89 pubmed
    The gene numb encodes for a protein (Numb) involved in cell fate decisions in Drosophila, with proposed endocytic and developmental functions in mammalians...
  8. Schmit T, Nihal M, Ndiaye M, Setaluri V, Spiegelman V, Ahmad N. Numb regulates stability and localization of the mitotic kinase PLK1 and is required for transit through mitosis. Cancer Res. 2012;72:3864-72 pubmed publisher
    b>Numb functions in progenitor cell fate determination and early development, but it is also expressed in postdevelopmental tissues and cancers where its role is unclear...
  9. Nishimura T, Kaibuchi K. Numb controls integrin endocytosis for directional cell migration with aPKC and PAR-3. Dev Cell. 2007;13:15-28 pubmed
    ..Here, we show that the endocytic adaptor protein Numb is an important component of the machinery for directional integrin trafficking in migrating cells...

More Information

Publications94

  1. Juven Gershon T, Shifman O, Unger T, Elkeles A, Haupt Y, Oren M. The Mdm2 oncoprotein interacts with the cell fate regulator Numb. Mol Cell Biol. 1998;18:3974-82 pubmed
    ..We report that in vitro and in transfected cells, Mdm2 can associate with Numb, a protein involved in the determination of cell fate...
  2. Euskirchen P, Skaftnesmo K, Huszthy P, Brekkå N, Bjerkvig R, Jacobs A, et al. NUMB does not impair growth and differentiation status of experimental gliomas. Exp Cell Res. 2011;317:2864-73 pubmed publisher
    The cell fate determinant NUMB orchestrates asymmetric cell division in flies and mammals and has lately been suggested to have a tumor suppressor function in breast and lung cancer...
  3. Smith C, Lau K, Rahmani Z, Dho S, Brothers G, She Y, et al. aPKC-mediated phosphorylation regulates asymmetric membrane localization of the cell fate determinant Numb. EMBO J. 2007;26:468-80 pubmed
    ..protein kinase C (aPKC) directs the polarized distribution and unequal segregation of the cell fate determinant Numb during asymmetric cell divisions...
  4. Verdi J, Bashirullah A, Goldhawk D, Kubu C, Jamali M, Meakin S, et al. Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage. Proc Natl Acad Sci U S A. 1999;96:10472-6 pubmed
    Neuronal cell fate decisions are directed in Drosophila by NUMB, a signaling adapter protein with two protein-protein interaction domains: a phosphotyrosine-binding domain and a proline-rich region (PRR) that functions as an SH3-binding ..
  5. Nishimura T, Yamaguchi T, Tokunaga A, Hara A, Hamaguchi T, Kato K, et al. Role of numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2. Mol Biol Cell. 2006;17:1273-85 pubmed
    b>Numb has been implicated in cortical neurogenesis during nervous system development, as a result of its asymmetric partitioning and antagonizing Notch signaling...
  6. Karaczyn A, Bani Yaghoub M, Tremblay R, Kubu C, Cowling R, Adams T, et al. Two novel human NUMB isoforms provide a potential link between development and cancer. Neural Dev. 2010;5:31 pubmed publisher
    We previously identified four functionally distinct human NUMB isoforms. Here, we report the identification of two additional isoforms and propose a link between the expression of these isoforms and cancer...
  7. Nishimura T, Fukata Y, Kato K, Yamaguchi T, Matsuura Y, Kamiguchi H, et al. CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth. Nat Cell Biol. 2003;5:819-26 pubmed
    ..Here, we identify Numb as a CRMP-2-interacting protein...
  8. Bechara E, Sebestyén E, Bernardis I, Eyras E, Valcarcel J. RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control cancer cell proliferation. Mol Cell. 2013;52:720-33 pubmed publisher
    ..We identify the Notch pathway regulator NUMB as a key target of these factors in the control of cell proliferation...
  9. Katoh M, Katoh M. NUMB is a break of WNT-Notch signaling cycle. Int J Mol Med. 2006;18:517-21 pubmed
    ..Notch signaling inhibitors, NUMB and NUMB-like (NUMBL), are docking proteins with PTB domain...
  10. Chen H, Chen X, Ye F, Lu W, Xie X. Symmetric division and expression of its regulatory gene Numb in human cervical squamous carcinoma cells. Pathobiology. 2009;76:149-54 pubmed publisher
    To investigate the mode of cell division and Numb expression in cervical squamous cells...
  11. Rennstam K, McMichael N, Berglund P, Honeth G, Hegardt C, Rydén L, et al. Numb protein expression correlates with a basal-like phenotype and cancer stem cell markers in primary breast cancer. Breast Cancer Res Treat. 2010;122:315-24 pubmed publisher
    Decreased expression of Numb, resulting in activation of the proto-oncogene Notch1 and reduction in the tumor suppressor p53, has been demonstrated in mammary carcinomas...
  12. Zhong W, Feder J, Jiang M, Jan L, Jan Y. Asymmetric localization of a mammalian numb homolog during mouse cortical neurogenesis. Neuron. 1996;17:43-53 pubmed
    During Drosophila neurogenesis, differential segregation of Numb is necessary for daughter cells of asymmetric divisions to adopt distinct fates, at least partly by biasing the Notch-mediated cell-cell interaction...
  13. Susini L, Passer B, Amzallag Elbaz N, Juven Gershon T, Prieur S, Privat N, et al. Siah-1 binds and regulates the function of Numb. Proc Natl Acad Sci U S A. 2001;98:15067-72 pubmed
    ..We report that Siah-1 interacts directly with and promotes the degradation of the cell fate regulator Numb. Siah-1-mediated Numb degradation leads to redistribution of endogenous cell-surface Notch to the cytoplasm and ..
  14. Salcini A, Confalonieri S, Doria M, Santolini E, Tassi E, Minenkova O, et al. Binding specificity and in vivo targets of the EH domain, a novel protein-protein interaction module. Genes Dev. 1997;11:2239-49 pubmed
    ..Among these interactors were the human homolog of NUMB, a developmentally reguated gene of Drosophila, and RAB, the cellular cofactor of the HIV REV protein...
  15. Calderwood D, Fujioka Y, de Pereda J, García Alvarez B, Nakamoto T, Margolis B, et al. Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling. Proc Natl Acad Sci U S A. 2003;100:2272-7 pubmed
    ..In addition to the known integrin-binding proteins, we found that Numb (a negative regulator of Notch signaling) and Dok-1 (a signaling adaptor involved in cell migration) and their ..
  16. Nie J, McGill M, Dermer M, Dho S, Wolting C, McGlade C. LNX functions as a RING type E3 ubiquitin ligase that targets the cell fate determinant Numb for ubiquitin-dependent degradation. EMBO J. 2002;21:93-102 pubmed
    LNX is a RING finger and PDZ domain containing protein that interacts with the cell fate determinant Numb. To investigate the function of LNX, we tested its RING finger domain for ubiquitin ligase activity...
  17. Yan B, Omar F, Das K, Ng W, Lim C, Shiuan K, et al. Characterization of Numb expression in astrocytomas. Neuropathology. 2008;28:479-84 pubmed publisher
    During early neurodevelopment, asymmetric segregation of Numb in mitotic progenitor cells influences the fate of daughter cells, whereby one daughter retains the progenitor phenotype while the other proceeds along a differentiation ..
  18. Amson R, Pece S, Lespagnol A, Vyas R, Mazzarol G, Tosoni D, et al. Reciprocal repression between P53 and TCTP. Nat Med. 2011;18:91-9 pubmed publisher
    ..Here we report a negative feedback loop between P53 and TCTP. TCTP promotes P53 degradation by competing with NUMB for binding to P53-MDM2-containing complexes...
  19. Dho S, Jacob S, Wolting C, French M, Rohrschneider L, McGlade C. The mammalian numb phosphotyrosine-binding domain. Characterization of binding specificity and identification of a novel PDZ domain-containing numb binding protein, LNX. J Biol Chem. 1998;273:9179-87 pubmed
    b>Numb is a phosphotyrosine-binding (PTB) domain-containing protein implicated in the control of cell fate decisions during development...
  20. Jiang X, Xing H, Kim T, Jung Y, Huang W, Yang H, et al. Numb regulates glioma stem cell fate and growth by altering epidermal growth factor receptor and Skp1-Cullin-F-box ubiquitin ligase activity. Stem Cells. 2012;30:1313-26 pubmed publisher
    ..Here, we show that asymmetric Numb localization specifies glioblastoma stem-like cell (GSC) fate in a manner that does not require Notch inhibition...
  21. Sato K, Watanabe T, Wang S, Kakeno M, Matsuzawa K, Matsui T, et al. Numb controls E-cadherin endocytosis through p120 catenin with aPKC. Mol Biol Cell. 2011;22:3103-19 pubmed publisher
    Cadherin trafficking controls tissue morphogenesis and cell polarity. The endocytic adaptor Numb participates in apicobasal polarity by acting on intercellular adhesions in epithelial cells...
  22. Uzdensky A, Demyanenko S, Fedorenko G, Lapteva T, Fedorenko A. Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex. Mol Neurobiol. 2017;54:4172-4188 pubmed publisher
    ..as protein kinase B?/GSK-3, protein kinase C and its ?1 and ?2 isoforms, Wnt/?-catenin (axin1, GSK-3, FRAT1), Notch/NUMB, DYRK1A, TDP43; mitochondria quality control (Pink1, parkin, HtrA2); ubiquitin-mediated proteolysis (ubiquilin-1, ..
  23. James K, Bhartiya D, Ganguly R, Kaushik A, Gala K, Singh P, et al. Gonadotropin and steroid hormones regulate pluripotent very small embryonic-like stem cells in adult mouse uterine endometrium. J Ovarian Res. 2018;11:83 pubmed publisher
    ..symmetric divisions and clonal expansion of stem/progenitor cells was confirmed by co-expression of OCT-4 and NUMB. Results confirm presence of VSELs and their regulation by circulatory hormones in mouse uterus...
  24. Fulop B, Sandor B, Szentléleky E, Karanyicz E, Reglodi D, Gaszner B, et al. Altered Notch Signaling in Developing Molar Teeth of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Deficient Mice. J Mol Neurosci. 2018;: pubmed publisher
    ..CBF1 humans/Su (H) Drosophila/LAG1 Caenorhabditis elegans transcription factor); TACE (TNF-? converting enzyme), NUMB] in molar teeth of 5-day-old WT, and homozygous and heterozygous PACAP-deficient mice...
  25. Schuring A, Dahlhues B, Korte A, Kiesel L, Titze U, Heitkötter B, et al. The endometrial stem cell markers notch-1 and numb are associated with endometriosis. Reprod Biomed Online. 2018;36:294-301 pubmed publisher
    ..This case-control study investigates an association of the endometrial stem cell markers notch-1 and numb with endometriosis...
  26. Hong J, Liu Z, Zhu H, Zhang X, Liang Y, Yao S, et al. The tumor suppressive role of NUMB isoform 1 in esophageal squamous cell carcinoma. Oncotarget. 2014;5:5602-14 pubmed
    ..To date, few biomarkers have been identified for ESCC. In present study, we found a tumor suppressor, NUMB isoform 1 (NUMB-1), as a promising prognostic biomarker for patients with ESCC. NUMB-1 mRNA was downregulated in 66...
  27. Lenihan J, Saha O, Young P. Proteomic analysis reveals novel ligands and substrates for LNX1 E3 ubiquitin ligase. PLoS ONE. 2017;12:e0187352 pubmed publisher
    Ligand of Numb protein X1 (LNX1) is an E3 ubiquitin ligase that contains a catalytic RING (Really Interesting New Gene) domain and four PDZ (PSD-95, DlgA, ZO-1) domains. LNX1 can ubiquitinate Numb, as well as a number of other ligands...
  28. Collins K, Kainov Y, Christodolou E, Ray D, Morris Q, Hughes T, et al. An RRM-ZnF RNA recognition module targets RBM10 to exonic sequences to promote exon exclusion. Nucleic Acids Res. 2017;45:6761-6774 pubmed publisher
    ..RRM2) of RBM10 recognizes a C-rich sequence, which explains its known interaction with the intronic 3΄ site of NUMB exon 9 contributing to regulation of the Notch pathway in cancer...
  29. Guo Y, Zhang K, Cheng C, Ji Z, Wang X, Wang M, et al. Numb-/low Enriches a Castration-Resistant Prostate Cancer Cell Subpopulation Associated with Enhanced Notch and Hedgehog Signaling. Clin Cancer Res. 2017;23:6744-6756 pubmed publisher
    b>Purpose: To elucidate the role and molecular mechanism of Numb in prostate cancer and the functional contribution of Numb-/low prostate cancer cells in castration resistance...
  30. Gui S, Teng L, Wang S, Liu S, Lin Y, Zhao X, et al. Overexpression of CXCL3 can enhance the oncogenic potential of prostate cancer. Int Urol Nephrol. 2016;48:701-9 pubmed publisher
    ..Finally, our data showed that exogenous CXCL3 can regulate the expression of genes including ERK, TP73, NUMB, BAX and NDRG3...
  31. Nöske K, Stark H, Nevaril L, Berning M, Langbein L, Goyal A, et al. Mitotic Diversity in Homeostatic Human Interfollicular Epidermis. Int J Mol Sci. 2016;17: pubmed publisher
    ..As a potential marker for asymmetric division, we investigated for Numb and found that it was evenly spread in almost all undifferentiated keratinocytes, but indeed asymmetrically ..
  32. Sapir T, Levy T, Kozer N, Shin I, Zamor V, Haffner Krausz R, et al. Notch Activation by Shootin1 Opposing Activities on 2 Ubiquitin Ligases. Cereb Cortex. 2017;:1-14 pubmed publisher
    ..propensity of activating the pathway either by interacting with LNX1/2 and promoting poly-ubiquitination of Numb or by complexing with Itch and impairing poly-ubiquitination of NICD...
  33. Birkeland M, Heir T. Making connections: exploring the centrality of posttraumatic stress symptoms and covariates after a terrorist attack. Eur J Psychotraumatol. 2017;8:1333387 pubmed publisher
    ..thoughts and nightmares, feeling easily startled and overly alert, and between feeling detached and emotionally numb. The most central symptom in the symptom network was feeling emotionally numb...
  34. Vora N, Haryee H, Dickson J, Miller R. Burkitt non-Hodgkin lymphoma presenting with mental neuropathy ('numb chin' syndrome) in an HIV-positive patient. Int J STD AIDS. 2017;:956462417742562 pubmed publisher
    ..A patient with virologically controlled human immunodeficiency virus (HIV) infection presented with a 'numb chin' on the background of long-standing night sweats, malaise and weight loss, worsening respiratory symptoms, and ..
  35. Wei J, Fu Z, Li P, Miao H, Li B, Ma Y, et al. The clathrin adaptor proteins ARH, Dab2, and numb play distinct roles in Niemann-Pick C1-Like 1 versus low density lipoprotein receptor-mediated cholesterol uptake. J Biol Chem. 2014;289:33689-700 pubmed publisher
    ..Another adaptor protein, Numb recognizes the endocytic motif in NPC1L1 C terminus and couples NPC1L1 to endocytic machinery...
  36. Hung P, Liu C, Chou C, Kao S, Yang C, Chang K, et al. miR-146a enhances the oncogenicity of oral carcinoma by concomitant targeting of the IRAK1, TRAF6 and NUMB genes. PLoS ONE. 2013;8:e79926 pubmed publisher
    ..miR-146a oncogenic activity is associated with down-regulation of IRAK1, TRAF6 and NUMB expression...
  37. Nayak D, Sivaraman J. Structure of LNX1:Ubc13~Ubiquitin Complex Reveals the Role of Additional Motifs for the E3 Ligase Activity of LNX1. J Mol Biol. 2018;430:1173-1188 pubmed publisher
    LNX1 (ligand of numb protein-X1) is a RING and PDZ domain-containing E3 ubiquitin ligase that ubiquitinates human c-Src kinase...
  38. Hope I, Morton K, Newlands C, Butler Manuel S, Madhuri T. Lockjaw from a metastatic uterine leiomyosarcoma- case report and review of the literature. BMC Womens Health. 2017;17:119 pubmed publisher
    ..6 months later she presented to A & E with a numb lower lip but it took another 6 months for the diagnosis of metastatic LMS to the mandible to be made...
  39. Patel H, Bhartiya D, Parte S. Further characterization of adult sheep ovarian stem cells and their involvement in neo-oogenesis and follicle assembly. J Ovarian Res. 2018;11:3 pubmed publisher
    ..Asymmetric cell division (ACD) was monitored by studying expression of OCT-4 and NUMB. Additional evidence was generated on the presence of two populations of stem cells in the OSE including VSELs and ..
  40. Swarnkar G, Chen T, Arra M, Nasir A, Mbalaviele G, Abu Amer Y. NUMBL Interacts with TAK1, TRAF6 and NEMO to Negatively Regulate NF-?B Signaling During Osteoclastogenesis. Sci Rep. 2017;7:12600 pubmed publisher
    NF-?B signaling is essential for osteoclast differentiation and skeletal homeostasis. We have reported recently that NUMB-like (NUMBL) protein modulates osteoclastogenesis by down regulating NF-?B activation...
  41. Shan Z, Tu Y, Yang Y, Liu Z, Zeng M, Xu H, et al. Basal condensation of Numb and Pon complex via phase transition during Drosophila neuroblast asymmetric division. Nat Commun. 2018;9:737 pubmed publisher
    ..In NBs, the cell fate determinant Numb forms a basal crescent together with Pon and is segregated into the basal daughter cell to initiate its ..
  42. Yogosawa S, Miyauchi Y, Honda R, Tanaka H, Yasuda H. Mammalian Numb is a target protein of Mdm2, ubiquitin ligase. Biochem Biophys Res Commun. 2003;302:869-72 pubmed
    Drosophila Numb protein functions as an antagonist against Notch signal. The expression of this protein is asymmetrical in divided cells and thought to be involved in the neural cell differentiation and/or cell fate...
  43. Toriya M, Tokunaga A, Sawamoto K, Nakao K, Okano H. Distinct functions of human numb isoforms revealed by misexpression in the neural stem cell lineage in the Drosophila larval brain. Dev Neurosci. 2006;28:142-55 pubmed
    Mammalian Numb (mNumb) has multiple functions and plays important roles in the regulation of neural development, including maintenance of neural progenitor cells and promotion of neuronal differentiation in the central nervous system (CNS)..
  44. Faraldo M, Glukhova M. Regulating the regulator: Numb acts upstream of p53 to control mammary stem and progenitor cell. J Cell Biol. 2015;211:737-9 pubmed publisher
    ..J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505037) report that cell fate determinant and tumor suppressor Numb imposes asymmetric cell divisions in mammary stem cells by regulating p53...
  45. Zhou L, Yang D, Wang D, Xie Y, Zhou J, Zhou L, et al. Numb deficiency in cerebellar Purkinje cells impairs synaptic expression of metabotropic glutamate receptor and motor coordination. Proc Natl Acad Sci U S A. 2015;112:15474-9 pubmed publisher
    Protein Numb, first identified as a cell-fate determinant in Drosophila, has been shown to promote the development of neurites in mammals and to be cotransported with endocytic receptors in clathrin-coated vesicles in vitro...
  46. Johnson S, Zitserman D, Roegiers F. Numb regulates the balance between Notch recycling and late-endosome targeting in Drosophila neural progenitor cells. Mol Biol Cell. 2016;27:2857-66 pubmed publisher
    ..We find that the endosomal adaptor protein Numb regulates levels of Notch receptor trafficking to Rab7-labeled late endosomes but not early endosomes...
  47. Kim H, Ronai Z. Rewired Notch/p53 by Numb'ing Mdm2. J Cell Biol. 2018;217:445-446 pubmed publisher
    ..pathways are known to control the tumor suppressor protein p53, coordinated regulation of the p53-Notch axis by Numb may have an even more remarkable impact. In this issue, Colaluca at al. (2018. J. Cell Biol. https://doi...
  48. Iguchi T, Nambara S, Masuda T, Komatsu H, Ueda M, Kidogami S, et al. miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients' Susceptibility to Liver Metastasis. PLoS ONE. 2016;11:e0165912 pubmed publisher
    miR-146a plays important roles in cancer as it directly targets NUMB, an inhibitor of Notch signaling. miR-146a is reportedly regulated by a G>C polymorphism (SNP; rs2910164)...
  49. Ma L, Wang L, Shan Y, Nafees M, Ihab E, Zhang R, et al. Suppression of cancer stemness by upregulating Ligand-of-Numb protein X1 in colorectal carcinoma. PLoS ONE. 2017;12:e0188665 pubmed publisher
    ..Therefore, identification of colorectal CSC regulators could provide promising targets for CRC. Ligand-of-Numb protein X1 (LNX1) is one E3 ubiquitin ligase which mediates the ubiquitination and degradation of Numb...
  50. Kudinov A, Karanicolas J, Golemis E, Boumber Y. Musashi RNA-Binding Proteins as Cancer Drivers and Novel Therapeutic Targets. Clin Cancer Res. 2017;23:2143-2153 pubmed publisher
    ..the mRNA stability and translation of proteins operating in essential oncogenic signaling pathways, including NUMB/Notch, PTEN/mTOR, TGFβ/SMAD3, MYC, cMET, and others...
  51. Liu C, Liu L, Chen X, Cheng J, Zhang H, Shen J, et al. Sox9 regulates self-renewal and tumorigenicity by promoting symmetrical cell division of cancer stem cells in hepatocellular carcinoma. Hepatology. 2016;64:117-29 pubmed publisher
    ..Sox9 also negatively regulates Numb expression, contributing to a feedback circuit that maintains Notch activity and directs symmetrical cell division...
  52. Esser S, Thurston M, Nalluri K, Muzaurieta A. "Numb-Leg" in a CrossFit Athlete: A Case Presentation. PM R. 2017;9:834-836 pubmed publisher
    ..v. ..
  53. Aerden T, Grisar K, Neven P, Hauben E, Politis C. Numb chin syndrome as a sign of mandibular metastasis: A case report. Int J Surg Case Rep. 2017;31:68-71 pubmed publisher
    ..A numb chin is an important presentation of oral metastasis, but other dental and systemic pathology may be involved...
  54. Mozūraitienė J, Bielskiene K, Atkocius V, Labeikyte D. Molecular alterations in signal pathways of melanoma and new personalized treatment strategies: Targeting of Notch. Medicina (Kaunas). 2015;51:133-145 pubmed publisher
    ..It is possible that restoration of p53-MDM2-NUMB complexes in melanoma can restore wild type p53 function and positively modulate Notch pathway...
  55. Haider M, Qiu Q, Bani Yaghoub M, Tsang B, Gruslin A. Characterization and role of NUMB in the human extravillous trophopblast. Placenta. 2011;32:441-9 pubmed publisher
    b>NUMB is a multifunctional protein involved in asymmetric cell differentiation, proliferation and maintenance...
  56. Dursun E, Gezen Ak D. Vitamin D receptor is present on the neuronal plasma membrane and is co-localized with amyloid precursor protein, ADAM10 or Nicastrin. PLoS ONE. 2017;12:e0188605 pubmed publisher
    ..E-cadherin interaction with APP or the ?-secretase complex may involve NOTCH1, NUMB, or FHL2, according to FpClass...
  57. Sentenská L, Müller C, Pekar S, Uhl G. Neurons and a sensory organ in the pedipalps of male spiders reveal that it is not a numb structure. Sci Rep. 2017;7:12209 pubmed publisher
    ..These findings provide a new framework for studies on reproductive behaviour and sexual selection in spiders. ..
  58. Tosoni D, Pambianco S, Ekalle Soppo B, Zecchini S, Bertalot G, Pruneri G, et al. Pre-clinical validation of a selective anti-cancer stem cell therapy for Numb-deficient human breast cancers. EMBO Mol Med. 2017;9:655-671 pubmed publisher
    The cell fate determinant Numb is frequently downregulated in human breast cancers (BCs), resulting in p53 inactivation and an aggressive disease course...
  59. Sun J, Wang K, Teng J, Yu Y, Hua R, Zhou H, et al. Numb had anti-tumor effects in prostatic cancer. Biomed Pharmacother. 2017;92:108-115 pubmed publisher
    The aim of this study was to explain the Numb anti-cancer effects in the prostatic cancer. Collecting the 20 prostatic cancer patients and analyzing the correlation between Numb and Glease score...
  60. Kansaku A, Hirabayashi S, Mori H, Fujiwara N, Kawata A, Ikeda M, et al. Ligand-of-Numb protein X is an endocytic scaffold for junctional adhesion molecule 4. Oncogene. 2006;25:5071-84 pubmed
    ..yeast two-hybrid screening to search for an unidentified JAM4-binding protein and obtained one isoform of Ligand-of-Numb protein X1 (LNX1), LNXp70, that is an interactor of Numb...
  61. Tian L, Li H, Jin B, Pan X, Man J, Zhang P, et al. MDM2 interacts with and downregulates a sarcomeric protein, TCAP. Biochem Biophys Res Commun. 2006;345:355-61 pubmed
    ..Further investigation will focus on the biological significance of MDM2-TCAP interaction in cardiac hypertrophy. ..
  62. Hwang W, Jiang J, Yang S, Huang T, Lan H, Teng H, et al. MicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer stem cells. Nat Cell Biol. 2014;16:268-80 pubmed publisher
    ..miR-146a targets Numb to stabilize β-catenin, which forms a feedback circuit to maintain Wnt activity and directs SCD...
  63. Yang S, Sheng L, Xu K, Wang Y, Zhu H, Zhang P, et al. Anticancer effect of quinacrine on diffuse large B?cell lymphoma via inhibition of MSI2?NUMB signaling pathway. Mol Med Rep. 2017;: pubmed publisher
    ..Upon exposure to QC, RNA?binding protein Musashi homolog 2 inactivation and activation of protein numb homolog were observed. In addition, QC was able to inhibit the expression of Myc proto?oncogene protein...
  64. Raimo M, Orso F, Grassi E, Cimino D, Penna E, De Pittà C, et al. miR-146a Exerts Differential Effects on Melanoma Growth and Metastatization. Mol Cancer Res. 2016;14:548-62 pubmed publisher
    ..It was determined that miR-146a coordinated melanoma cell growth by its direct targets lunatic fringe (LFNG) and NUMB, which operate on the NOTCH/PTEN/Akt pathway; while inhibition of metastasis formation was linked to decreased ..
  65. García Heredia J, Lucena Cacace A, Verdugo Sivianes E, Pérez M, Carnero A. The Cargo Protein MAP17 (PDZK1IP1) Regulates the Cancer Stem Cell Pool Activating the Notch Pathway by Abducting NUMB. Clin Cancer Res. 2017;23:3871-3883 pubmed publisher
    ..b>Results: MAP17 (PDZKIP1), a small cargo protein overexpressed in tumors, interacts with NUMB through the PDZ-binding domain activating the Notch pathway, leading to an increase in stem cell factors and cancer-..
  66. Krieger J, Taylor P, Moran M, McGlade C. Comprehensive identification of phosphorylation sites on the Numb endocytic adaptor protein. Proteomics. 2015;15:434-46 pubmed publisher
    b>Numb is an adaptor protein that functions in the endocytosis and intracellular trafficking of membrane receptors and adhesion molecules...
  67. Xie C, Lu Z, Liu G, Fang Y, Liu J, Huang Z, et al. Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma. Int J Mol Med. 2015;36:653-60 pubmed publisher
    b>Numb, an endocytic adaptor, is a known cell fate determinant that participates in asymmetric cell division. The present study aimed to explore the potential roles of Numb in hepatocarcinogenesis...
  68. Zheng K, He T, Ji W, Jiang H, Shen Y, Li G, et al. Alternative splicing of NUMB, APP and VEGFA as the features of pancreatic ductal carcinoma. Int J Clin Exp Pathol. 2015;8:6181-91 pubmed
    ..Here we report our discovery on the correlations between transcriptional alternative splicing (AS) of NUMB, APP, VEGFA and PDAC in patients. The expression of NUMB, APP, VEGFA from patient samples was determined by qRT-PCR...
  69. Shao X, Ding Z, Zhao M, Liu K, Sun H, Chen J, et al. Mammalian Numb protein antagonizes Notch by controlling postendocytic trafficking of the Notch ligand Delta-like 4. J Biol Chem. 2017;292:20628-20643 pubmed publisher
    The biological antagonism between the signaling proteins Numb and Notch has been implicated in the regulation of many developmental processes, especially in asymmetric cell division...
  70. Sun H, Liu Y, Zhang L, Shao X, Liu K, Ding Z, et al. Numb positively regulates autophagic flux via regulating lysosomal function. Biochem Biophys Res Commun. 2017;491:780-786 pubmed publisher
    ..Here, using genetic knockdown, we uncover the role of Numb, an endocytic adaptor protein, in regulating the late steps of autophagy...
  71. Chastagner P, Israel A, Brou C. AIP4/Itch regulates Notch receptor degradation in the absence of ligand. PLoS ONE. 2008;3:e2735 pubmed publisher
    ..Taken together our results identify a specific step of Notch regulation in the absence of any activation and underline differences between mammalian and Drosophila Notch pathways. ..
  72. Rajendran D, Zhang Y, Berry D, McGlade C. Regulation of Numb isoform expression by activated ERK signaling. Oncogene. 2016;35:5202-13 pubmed publisher
    The endocytic adaptor protein Numb has a major role in development as an intrinsic regulator of cell fate determination and inhibitor of the Notch signaling pathway...
  73. Chen J, Xu J, Zhao W, Hu G, Cheng H, Kang Y, et al. Characterization of human LNX, a novel ligand of Numb protein X that is downregulated in human gliomas. Int J Biochem Cell Biol. 2005;37:2273-83 pubmed
    Gliomas are major tumors of the central nervous system with a wide spectrum of different tumor types. Ligand of Numb protein X (LNX) is PDZ domain containing protein that interacts with cell fate determinant Numb...
  74. Colaluca I, Basile A, Freiburger L, D Uva V, Disalvatore D, Vecchi M, et al. A Numb-Mdm2 fuzzy complex reveals an isoform-specific involvement of Numb in breast cancer. J Cell Biol. 2018;217:745-762 pubmed publisher
    b>Numb functions as an oncosuppressor by inhibiting Notch signaling and stabilizing p53. This latter effect depends on the interaction of Numb with Mdm2, the E3 ligase that ubiquitinates p53 and commits it to degradation...
  75. Wang J, Sun Z, Liu Y, Kong L, Zhou S, Tang J, et al. Comparison of tumor biology of two distinct cell sub-populations in lung cancer stem cells. Oncotarget. 2017;8:96852-96864 pubmed publisher
    ..to undergo asymmetric division was visualized and quantified by the asymmetric segregation of labeled BrdU and NUMB to one of the two daughter cells in anaphase cell division...
  76. Kikuchi H, Sakakibara Konishi J, Furuta M, Yokouchi H, Nishihara H, Yamazaki S, et al. Expression of Notch1 and Numb in small cell lung cancer. Oncotarget. 2017;8:10348-10358 pubmed publisher
    Notch signaling in tumorigenesis functions as an oncogene or tumor suppressor according to the type of malignancy. Numb represses intracellular Notch signaling...
  77. Lin Y, Barske L, DeFalco T, Capel B. Numb regulates somatic cell lineage commitment during early gonadogenesis in mice. Development. 2017;144:1607-1618 pubmed publisher
    ..We found that NUMB is asymmetrically localized in CE cells, suggesting that it might be involved...
  78. Mu Y, Zhang X, Fan W, Li X, Chen G, Chen J, et al. [Mechanism of Astragaloside prevents cholestatic liver fibrosis through inhibition of Notch signaling activation]. Zhonghua Gan Zang Bing Za Zhi. 2017;25:575-582 pubmed publisher
    ..was evaluated by analyzing expressions of Notch-1, -2, -3, -4, Jagged (JAG)1, Delta like (DLL)-1, -3, -4, Hes1, Numb and RBP-J?. Statistical analysis of variance analysis, q test, P < 0...
  79. Asquith C, Laitinen T, Bennett J, Godoi P, East M, Tizzard G, et al. Identification and Optimization of 4-Anilinoquinolines as Inhibitors of Cyclin G Associated Kinase. ChemMedChem. 2017;: pubmed publisher
    ..produced GAK inhibitors with nanomolar activity, over 50,000-fold selectivity relative to other members of the numb-associated kinase (NAK) sub-family, and a compound (49) with a narrow spectrum kinome profile...
  80. Sajadimajd S, Yazdanparast R, Akram S. Involvement of Numb-mediated HIF-1α inhibition in anti-proliferative effect of PNA-antimiR-182 in trastuzumab-sensitive and -resistant SKBR3 cells. Tumour Biol. 2016;37:5413-26 pubmed publisher
    ..of NICD, Hes1, HIF-1α, and p-Akt in both cell groups, while it augmented the intracellular content of FOXO1 and Numb suppressor proteins...
  81. Hirai M, Arita Y, McGlade C, Lee K, Chen J, Evans S. Adaptor proteins NUMB and NUMBL promote cell cycle withdrawal by targeting ERBB2 for degradation. J Clin Invest. 2017;127:569-582 pubmed publisher
    ..Here, we have found that the endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2 signaling in maturing trabeculae...
  82. Lei C, Tang H, Ye C, You C, Zhang J, Zhang C, et al. MDM2 Contributes to High Glucose-Induced Glomerular Mesangial Cell Proliferation and Extracellular Matrix Accumulation via Notch1. Sci Rep. 2017;7:10393 pubmed publisher
    ..However, Numb, a substrate of MDM2 which suppresses Notch1 signaling, was found not to be involved in the MDM2 and Notch1 ..
  83. Shao C, Chien S, Farah E, Li Z, Ahmad N, Liu X. Plk1 phosphorylation of Numb leads to impaired DNA damage response. Oncogene. 2017;: pubmed publisher
    Although Numb is well-recognized as a cell-fate determinant in stem/progenitor cells, accumulating evidence supports that Numb also has a critical role in adult tissues and cancers, in particular, in the context of regulation of tumor ..
  84. Zhang J, Shao X, Sun H, Liu K, Ding Z, Chen J, et al. NUMB negatively regulates the epithelial-mesenchymal transition of triple-negative breast cancer by antagonizing Notch signaling. Oncotarget. 2016;7:61036-61053 pubmed publisher
    ..Here, we report that NUMB is a negative regulator of EMT in both human mammary epithelial cells and breast cancer cells...
  85. Feldman M. Editorial Commentary: My Shoulder Feels Great, But Why Is My Thigh Numb? Lateral Femoral Cutaneous Nerve Injury After Shoulder Arthroscopy in the Beach Chair Position. Arthroscopy. 2017;33:1963-1964 pubmed publisher
    ..Taking an extra minute to ensure a safe beach chair position will likely minimize the occurrence and prevent a disheartening conversation at the first postoperative visit...