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Given the apparent absence of major NUMB dysfunction in LNX (zeige LNX1 Proteine) null animals
Data suggest that Numb acts as a Notch (zeige NOTCH1 Proteine) antagonist by controlling intracellular destination and stability of the Notch ligand (zeige JAG2 Proteine) Delta-like (zeige DLK1 Proteine) 4 (DLL4 (zeige DLL4 Proteine)) through a post-endocytic sorting process; Numb negatively controls DLL4 (zeige DLL4 Proteine) plasma membrane recycling through well-documented recycling regulator protein AP1 (zeige JUN Proteine).
NUMB is necessary for establishing polarity in coelomic epithelium cells.
investigations revealed that NUMB and NUMBL (zeige NUMBL Proteine) interacted with small GTPase (zeige RACGAP1 Proteine) Rab7 (zeige RAB7A Proteine) to transition ERBB2 (zeige ERBB2 Proteine) from early to late endosome for degradation.
These findings highlight the importance of Numb and Numbl (zeige NUMBL Proteine) in the control of myoepithelial cell fate determination, epithelial identity, and lactogenesis
RBM4 (zeige RBM4 Proteine) depletion reduced the expression of the proneural gene Mash1 (zeige ASCL1 Proteine), and such reduction was reversed by an RBM4 (zeige RBM4 Proteine)-induced Numb isoform containing exon 3 but lacking exon 9. RBM4 (zeige RBM4 Proteine) was also essential for neurite outgrowth from cortical neurons in vitro. Neurite outgrowth defects of RBM4 (zeige RBM4 Proteine)-depleted neurons were rescued by RBM4 (zeige RBM4 Proteine)-induced exon 9-lacking Numb isoforms. RBM4 (zeige RBM4 Proteine) modulates exon selection of Numb.
role in the mediation of TCR degradation
miR (zeige MLXIP Proteine)-34a directly suppresses Numb in early-stage colon cancer stem cells (CCSCs), forming an incoherent feedforward loop (IFFL) targeting Notch (zeige NOTCH1 Proteine) 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 (zeige TLR4 Proteine).
Loss of Numb induces a p53 (zeige TP53 Proteine)-dependent senescence following skeletal muscle injury.
Numb is associated with modulation of Notch (zeige NOTCH1 Proteine)-driven epithelial-mesenchymal transition.
Numb(-/low) prostate cancer cells were smaller and quiescent, preferentially expressed Notch (zeige NOTCH1 Proteine) and Hedgehog (zeige SHH Proteine) downstream and stem-cell-associated genes, and associated with a greater resistance to androgen-deprivation therapy
MAP17 (zeige PDZK1IP1 Proteine) overexpression activates Notch (zeige NOTCH1 Proteine) pathway by sequestering NUMB. High levels of MAP17 (zeige PDZK1IP1 Proteine) correlated with tumorsphere formation and Notch (zeige NOTCH1 Proteine) and Stem gene transcription. Its direct modification causes direct alteration of tumorsphere number and Notch (zeige NOTCH1 Proteine) and Stem pathway transcription
NUMB has a role in negatively regulating the epithelial-mesenchymal transition of triple-negative breast cancer by antagonizing Notch (zeige NOTCH1 Proteine) signaling
In the present study, we identified that the adaptor protein Numb, which is demonstrated to be a novel binding partner of NEDD4-1 (zeige NEDD4 Proteine), plays important roles in controlling PTEN ubiquitination through regulating NEDD4-1 (zeige NEDD4 Proteine) activity and the association between PTEN and NEDD4-1 (zeige NEDD4 Proteine).
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