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Given the apparent absence of major NUMB dysfunction in LNX (show LNX1 Proteins) null animals
Data suggest that Numb acts as a Notch (show NOTCH1 Proteins) antagonist by controlling intracellular destination and stability of the Notch ligand (show JAG2 Proteins) Delta-like (show DLK1 Proteins) 4 (DLL4 (show DLL4 Proteins)) through a post-endocytic sorting process; Numb negatively controls DLL4 (show DLL4 Proteins) plasma membrane recycling through well-documented recycling regulator protein AP1 (show JUN Proteins).
NUMB is necessary for establishing polarity in coelomic epithelium cells.
investigations revealed that NUMB and NUMBL (show NUMBL Proteins) interacted with small GTPase (show RACGAP1 Proteins) Rab7 (show RAB7A Proteins) to transition ERBB2 (show ERBB2 Proteins) from early to late endosome for degradation.
These findings highlight the importance of Numb and Numbl (show NUMBL Proteins) in the control of myoepithelial cell fate determination, epithelial identity, and lactogenesis
RBM4 (show RBM4 Proteins) depletion reduced the expression of the proneural gene Mash1 (show ASCL1 Proteins), and such reduction was reversed by an RBM4 (show RBM4 Proteins)-induced Numb isoform containing exon 3 but lacking exon 9. RBM4 (show RBM4 Proteins) was also essential for neurite outgrowth from cortical neurons in vitro. Neurite outgrowth defects of RBM4 (show RBM4 Proteins)-depleted neurons were rescued by RBM4 (show RBM4 Proteins)-induced exon 9-lacking Numb isoforms. RBM4 (show RBM4 Proteins) modulates exon selection of Numb.
role in the mediation of TCR degradation
miR (show MLXIP Proteins)-34a directly suppresses Numb in early-stage colon cancer stem cells (CCSCs), forming an incoherent feedforward loop (IFFL) targeting Notch (show NOTCH1 Proteins) to separate stem and non-stem cell fates robustly.
Novel Role of Numb as A Regulator of Pro-inflammatory Cytokine Production in Macrophages in Response to Toll-like Receptor 4 (show TLR4 Proteins).
Loss of Numb induces a p53 (show TP53 Proteins)-dependent senescence following skeletal muscle injury.
Numb is associated with modulation of Notch (show NOTCH1 Proteins)-driven epithelial-mesenchymal transition.
Numb(-/low) prostate cancer cells were smaller and quiescent, preferentially expressed Notch (show NOTCH1 Proteins) and Hedgehog (show SHH Proteins) downstream and stem-cell-associated genes, and associated with a greater resistance to androgen-deprivation therapy
MAP17 (show PDZK1IP1 Proteins) overexpression activates Notch (show NOTCH1 Proteins) pathway by sequestering NUMB. High levels of MAP17 (show PDZK1IP1 Proteins) correlated with tumorsphere formation and Notch (show NOTCH1 Proteins) and Stem gene transcription. Its direct modification causes direct alteration of tumorsphere number and Notch (show NOTCH1 Proteins) and Stem pathway transcription
NUMB has a role in negatively regulating the epithelial-mesenchymal transition of triple-negative breast cancer by antagonizing Notch (show NOTCH1 Proteins) signaling
In the present study, we identified that the adaptor protein Numb, which is demonstrated to be a novel binding partner of NEDD4-1 (show NEDD4 Proteins), plays important roles in controlling PTEN ubiquitination through regulating NEDD4-1 (show NEDD4 Proteins) activity and the association between PTEN and NEDD4-1 (show NEDD4 Proteins).
Numb expression is not associated with favorable prognosis in small cell lung cancer.
Data suggest that over-expression of NUMB has anti-cancer effects to prostatic cancer cells; these studies included experiments both in vitro and in vivo (xenograft experiments in nude mice).
Using patient-derived xenografts, the study shows that expansion of the cancer stem cells pool, due to altered self-renewing divisions, is also a feature of Numb-deficient human breast cancers .
Numb binds to another docking regulator, Mon1b, and is required for the recruitment of cytosolic Mon1b to the early endosomes membrane.
Low NUMB expression is associated with pancreatic cancer.
The protein encoded by this gene plays a role in the determination of cell fates during development. The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1. Four transcript variants encoding different isoforms have been found for this gene.
protein numb homolog
, numb gene homolog