NUMB Localizes in the Basal Cortex of Mitotic Avian Neuroepithelial Cells and Modulates Neuronal Differentiation by Binding to NOTCH-1

Wakamatsu, Yoshio; Maynard, Thomas M.; Jones, Sonya U; Weston, James A.

doi:10.1016/s0896-6273(00)80754-0

Cited by 238 publications

(249 citation statements)

References 51 publications

Supporting

Mentioning

227

Contrasting

Unclassified

Order By: Relevance

“…In mammals, MSH1 is selectively expressed in neural progenitor cells (Okano et al, 2002) and is involved in cellular differentiation and tumorigenesis. In stem cells, MSH1 maintains the cells in an undifferentiated state through post-transcriptional inhibition of NUMB expression ), which in turn acts as an intracellular Notch antagonist and is involved in regulation of neuronal differentiation (Wakamatsu et al, 1999). Accordingly, MSH1 is considered a positive regulator of Notch signaling.…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridization

et al. 2004

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridization

et al. 2004

View full text Add to dashboard Cite

“…In Drosophila embryos, overexpression or deletion of Numb produces opposite phenotypes (26), reflecting a switch in cell fate specification. Similarly overexpression of avian Numb in the neuroepithelium promotes neurogenesis (27), and loss of Numb in the developing nervous system of the mouse embryos impairs the ability of progenitor cells to undergo asymmetric division producing a neuronal daughter and another progenitor cell (28). Since the presence of Numb protein in a cell influences its identity, understanding how the cellular levels of Numb are regulated is important to the elucidation of its function in asymmetric cell division.…”

Section: Discussionmentioning

confidence: 99%

A Novel PTB-PDZ Domain Interaction Mediates Isoform-specific Ubiquitylation of Mammalian Numb

Nie

McGlade

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

LNX was originally cloned as a Numb PTB-binding molecule, and it was subsequently found to act as a RING finger-type E3 ubiquitin ligase for the ubiquitylation and degradation of mNumb. Numb is a PTB domaincontaining protein that functions as an intrinsic determinant of cell fate in asymmetric cell division. In mammals, four protein isoforms arise from alternative mRNA splicing. Here we report that while all four protein isoforms bind to LNX, only p72 and p66 Numb isoforms are ubiquitylated and degraded. The p72 and p66 Numb proteins differ from the other two isoforms by the presence of an 11-amino acid sequence insert in the PTB domain (PTBi). We demonstrate that the isoform-specific ubiquitylation of mNumb is due to a novel interaction between the first PDZ domain (PDZ1) of LNX and the PTBi variant. Deletion of LNX PDZ1 domain resulted in loss of ubiquitylation and subsequent degradation of the PTBi form of Numb. Interestingly efficient PTBi ubiquitylation not only depends on association with the LNX PDZ1 domain but also requires binding to the canonical PTB-binding motif NPAY in LNX. Thus two distinct modes of PTBi-mediated interaction with LNX work in concert to allow the effective and specific degradation of the p72 and p66 isoforms of mNumb.Controlled protein degradation mediated by ubiquitin-dependent proteolysis underlies the regulation of many critical biological events during the life and death of a cell as well as in health and disease (1). Ubiquitylation of a target protein is achieved through a cascade involving at least three enzymes, namely E1, 1 E2, and E3, which activate and transfer ubiquitin to the substrate in a sequential manner. Polyubiquitylated proteins are recognized by the 26 S proteasome and are subsequently degraded into small peptides (2, 3).E3 ubiquitin ligases are responsible for the specific recognition of a multitude of substrates. Two major classes of E3 have been identified to date characterized by the presence of either a HECT (homologous to E6-AP carboxyl terminus) domain or a RING finger domain. HECT-type E3s catalyze ubiquitylation of a substrate by first forming an E3-ubiquitin thioester intermediate followed by the direct transfer of ubiquitin onto the substrate. On the other hand, RING-type E3s function as scaffolds that bring together the E2 and the target substrate to facilitate efficient transfer of the activated ubiquitin moiety from the E2 to the substrate protein (4). In addition to HECT or RING finger domains, E3 ligases also contain protein interaction modules for substrate recognition. Diversity in the repertoire of E3 substrate selection is achieved by linking a variety of protein interaction modules to the HECT or RING domains. For example, many HECT domain-containing E3s share the WW domain, which is involved in protein-protein interactions and has a role in targeting substrates containing a PY motif for ubiquitylation (5, 6). The RING-type E3 family is composed of two distinct groups, single and multisubunit proteins. Single subunit E3s such as c-Cbl contain...

show abstract

“…The molecules so far identified, such as Notch, Numb, Miranda, Staufen, and Prospero (10,20,45,46), have been shown to exhibit either basal or apical ''capping'' before division in static studies. Importantly, the fate molecule parcellation model only works in conjunction with variable orientations of the final cleavage plane.…”

Section: Cleavage Plane Orientation Does Not Always Predict Daughter mentioning

confidence: 99%

“…Thus, our data are incompatible with long-range or broad external controls and suggest that either short range (i.e., cell-contact-mediated) or intrinsic pathways specify the change in mode of division during neurogenesis. Furthermore, several studies have shown that contiguous VZ cells are likely clonally related (10,20,(45)(46)(47)(48) and are gap junction-coupled (49). Examples such as in Movie 3, where neighboring cells divide in opposite orientations, therefore suggest the possibility that clonally related cells, even those synchronized with respect to cell cycle phase, possess the ability to divide in different modes.…”

Section: Cleavage Plane Orientation Does Not Always Predict Daughter mentioning

confidence: 99%

Mitotic spindle rotation and mode of cell division in the developing telencephalon

Haydar

Ang

Rakić

2003

Proc. Natl. Acad. Sci. U.S.A.

224

187

View full text Add to dashboard Cite

The mode of neural stem cell division in the forebrain proliferative zones profoundly influences neocortical growth by regulating the number and diversity of neurons and glia. Long-term time-lapse multiphoton microscopy of embryonic mouse cortex reveals new details of the complex three-dimensional rotation and oscillation of the mitotic spindle before stem cell division. Importantly, the duration and amplitude of spindle movement predicts and specifies the eventual mode of mitotic division. These technological advances have provided dramatic data and insights into the kinetics of neural stem cell division by elucidating the involvement of spindle rotation in selection of the cleavage plane and the mode of neural stem cell division that together determine the size of the mammalian neocortex.T he number and diversity of cells in the cerebral cortex is due, in great measure, to the mode of progenitor cell division in the proliferative ventricular zone (VZ) before birth (1-4). At each mitotic division, the proliferative fate of each daughter cell, either reentering or exiting the cell cycle, dramatically influences neocortical growth (5). Symmetrical founder cell divisions, which predominate early, yield more progenitors and lead to an exponential expansion of the VZ population. In contrast, asymmetrical divisions, which prevail during later stages of neurogenesis, lead to cell commitment and diversity of the cortical architecture (1). Critical parameters of cortical growth are, therefore, the duration of the early symmetrical division phase and the time and extent of the transition to the asymmetrical mode of division (1-3). Despite the importance of this developmental strategy for brain growth, it is unknown how conversion between these major types of mitotic divisions is achieved in the VZ of the mammalian forebrain.The current model for how different daughter cell fates result from asymmetric stem cell divisions assumes that cytoplasmic fate-determining molecules are unequally distributed during mother cell mitosis (6-9). This asymmetrical segregation can initiate diverse cellular programs during development of the daughter cells, including restriction of potential and differentiation (10-13). A prerequisite for producing asymmetric allocation of intracellular contents, observed in rodent telencephalon, is rotation and alignment of the mitotic spindle before division (14). Supporting such a causative role in cell fate determination, spindle movement before anaphase and the choice of the final cleavage plane has been correlated with daughter cell behavior in both invertebrates (6, 15-19) and vertebrates (refs. 10, 13, 20, and 21; see Fig. 1). In mammalian studies, however, determination of the molecular mechanisms linking spindle orientation, parcellation of intracellular factors, and fate determination has suffered from the lack of an intact model system. We sought to develop the capability for real-time analysis of these issues in living tissue that preserves the three-dimensional relationship between stem and ...

show abstract

NUMB Localizes in the Basal Cortex of Mitotic Avian Neuroepithelial Cells and Modulates Neuronal Differentiation by Binding to NOTCH-1

Cited by 238 publications

References 51 publications

Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridization

Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridization

A Novel PTB-PDZ Domain Interaction Mediates Isoform-specific Ubiquitylation of Mammalian Numb

Mitotic spindle rotation and mode of cell division in the developing telencephalon

Contact Info

Product

Resources

About