DLL3 Antibody (Rabbit mAb) [A8D4] Datasheet

Biological Description

Specificity	DLL3 Antibody (Rabbit mAb) [A8D4] detects endogenous levels of total DLL3 protein.
Background	DLL3 is a divergent member of the DSL family of Notch ligands that, unlike canonical Delta and Jagged ligands, does not activate Notch signaling in neighboring cells but instead inhibits Notch signaling when expressed within the same cell as the receptor. Dll3 protein is not presented on the surface of presomitic mesoderm cells during embryonic development but instead interacts with Notch1 within the late endocytic compartment, targeting newly synthesized Notch1 for lysosomal degradation before the receptor undergoes post-translational processing and reaches the cell surface. This intracellular, cis-acting mechanism depletes the pool of Notch1 available for trans-activation by ligands on adjacent cells, and juxtaposition of Dll3 protein with sites of active Notch1 signaling in the presomitic mesoderm supports this inhibitory role during somite formation. Mutations in DLL3 disrupt this cis-inhibitory mechanism and cause spondylocostal dysostosis, a congenital disorder of vertebral segmentation, and targeted deletion of Dll3 in mice reproduces the somite segmentation defect and consequent vertebral malformation seen in the human disease. DLL3 is also a downstream transcriptional target of the proneural transcription factor ASCL1, and this regulatory relationship results in DLL3 being expressed on the surface of small cell lung cancer and other neuroendocrine tumor cells while remaining minimally expressed in normal adult tissues. An antibody-drug conjugate directed against surface DLL3 induces durable regression of patient-derived small cell lung cancer and large cell neuroendocrine carcinoma xenografts and selectively depletes tumor-initiating cells within these models, establishing DLL3's tumor-restricted surface expression as the basis for its use as a therapeutic target in high-grade pulmonary neuroendocrine cancers.

Specificity

DLL3 Antibody (Rabbit mAb) [A8D4] detects endogenous levels of total DLL3 protein.

Background

DLL3 is a divergent member of the DSL family of Notch ligands that, unlike canonical Delta and Jagged ligands, does not activate Notch signaling in neighboring cells but instead inhibits Notch signaling when expressed within the same cell as the receptor. Dll3 protein is not presented on the surface of presomitic mesoderm cells during embryonic development but instead interacts with Notch1 within the late endocytic compartment, targeting newly synthesized Notch1 for lysosomal degradation before the receptor undergoes post-translational processing and reaches the cell surface. This intracellular, cis-acting mechanism depletes the pool of Notch1 available for trans-activation by ligands on adjacent cells, and juxtaposition of Dll3 protein with sites of active Notch1 signaling in the presomitic mesoderm supports this inhibitory role during somite formation. Mutations in DLL3 disrupt this cis-inhibitory mechanism and cause spondylocostal dysostosis, a congenital disorder of vertebral segmentation, and targeted deletion of Dll3 in mice reproduces the somite segmentation defect and consequent vertebral malformation seen in the human disease. DLL3 is also a downstream transcriptional target of the proneural transcription factor ASCL1, and this regulatory relationship results in DLL3 being expressed on the surface of small cell lung cancer and other neuroendocrine tumor cells while remaining minimally expressed in normal adult tissues. An antibody-drug conjugate directed against surface DLL3 induces durable regression of patient-derived small cell lung cancer and large cell neuroendocrine carcinoma xenografts and selectively depletes tumor-initiating cells within these models, establishing DLL3's tumor-restricted surface expression as the basis for its use as a therapeutic target in high-grade pulmonary neuroendocrine cancers.

Usage Information

Application

WB, IP, IHC, IF, FCM

Dilution

WB	IP	IHC	IF	FCM
1:1000	1:30	1:100	1:100	1:600

Reactivity

Mouse, Human

Source

Rabbit Monoclonal Antibody

MW

65 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

References

https://pubmed.ncbi.nlm.nih.gov/21147753/
https://pubmed.ncbi.nlm.nih.gov/26311731/

DLL3 Antibody (Rabbit mAb) [A8D4]

Biological Description

Usage Information

References

Application Data