Datasheet

生物学的記述

Specificity	DcR1 Antibody (Rabbit mAb) [G21E20] detects endogenous levels of total DcR1 proteins.
Background	DcR1 (decoy receptor 1, also called TRAIL-R3 or TRID) is a cell-surface receptor for TRAIL (TNF-related apoptosis-inducing ligand), a member of the tumor necrosis factor family that activates rapid apoptosis in tumor cells through the death-signaling receptors DR4 and DR5. Unlike DR4 and DR5, which contain a cytoplasmic death domain required to transmit the pro-apoptotic signal following TRAIL engagement, DcR1 is anchored to the plasma membrane through a glycophospholipid anchor and lacks any cytoplasmic domain at all, and functional testing established that DcR1 binds TRAIL yet fails to transmit an apoptotic signal, instead acting as a decoy that inhibits TRAIL-induced cell death; consistent with this, treating porcine ovarian granulosa cells with phosphatidylinositol-specific phospholipase C to enzymatically cleave and remove surface DcR1 increased the number of cells undergoing TRAIL-induced apoptosis, directly confirming that intact, membrane-anchored DcR1 actively protects these cells from TRAIL-mediated death rather than merely lacking pro-apoptotic capacity by default. Comparing DcR1 with the second decoy receptor, DcR2 (which retains a truncated, non-functional death domain), reveals that the two decoys inhibit TRAIL signaling through mechanistically distinct routes: DcR1 prevents assembly of the death-inducing signaling complex (DISC) altogether by titrating and sequestering TRAIL molecules within lipid raft membrane microdomains before they can engage DR4 or DR5, whereas DcR2 is instead co-recruited together with DR5 directly into the forming DISC, where it interferes with activation of the initiator caspase and additionally blocks recruitment of DR4 into the DR5-containing complex. Because loss of DcR1 expression removes this ligand-sequestering brake and sensitizes cells to TRAIL-induced apoptosis, DcR1 downregulation is observed in tissues undergoing programmed cell death, such as atretic ovarian follicles, while conversely, tumor and stromal cells that retain or upregulate DcR1 can use it to blunt TRAIL sensitivity, and DcR1 expressed on stromal cells within the tumor microenvironment can exert this protective, TRAIL-sequestering effect even on neighboring tumor cells in trans, extending DcR1's inhibitory action beyond the cell expressing it. This dual cell-autonomous and microenvironmental decoy mechanism is considered a contributing factor in tumor resistance to TRAIL-based therapeutic strategies.

Specificity

DcR1 Antibody (Rabbit mAb) [G21E20] detects endogenous levels of total DcR1 proteins.

Background

DcR1 (decoy receptor 1, also called TRAIL-R3 or TRID) is a cell-surface receptor for TRAIL (TNF-related apoptosis-inducing ligand), a member of the tumor necrosis factor family that activates rapid apoptosis in tumor cells through the death-signaling receptors DR4 and DR5. Unlike DR4 and DR5, which contain a cytoplasmic death domain required to transmit the pro-apoptotic signal following TRAIL engagement, DcR1 is anchored to the plasma membrane through a glycophospholipid anchor and lacks any cytoplasmic domain at all, and functional testing established that DcR1 binds TRAIL yet fails to transmit an apoptotic signal, instead acting as a decoy that inhibits TRAIL-induced cell death; consistent with this, treating porcine ovarian granulosa cells with phosphatidylinositol-specific phospholipase C to enzymatically cleave and remove surface DcR1 increased the number of cells undergoing TRAIL-induced apoptosis, directly confirming that intact, membrane-anchored DcR1 actively protects these cells from TRAIL-mediated death rather than merely lacking pro-apoptotic capacity by default. Comparing DcR1 with the second decoy receptor, DcR2 (which retains a truncated, non-functional death domain), reveals that the two decoys inhibit TRAIL signaling through mechanistically distinct routes: DcR1 prevents assembly of the death-inducing signaling complex (DISC) altogether by titrating and sequestering TRAIL molecules within lipid raft membrane microdomains before they can engage DR4 or DR5, whereas DcR2 is instead co-recruited together with DR5 directly into the forming DISC, where it interferes with activation of the initiator caspase and additionally blocks recruitment of DR4 into the DR5-containing complex. Because loss of DcR1 expression removes this ligand-sequestering brake and sensitizes cells to TRAIL-induced apoptosis, DcR1 downregulation is observed in tissues undergoing programmed cell death, such as atretic ovarian follicles, while conversely, tumor and stromal cells that retain or upregulate DcR1 can use it to blunt TRAIL sensitivity, and DcR1 expressed on stromal cells within the tumor microenvironment can exert this protective, TRAIL-sequestering effect even on neighboring tumor cells in trans, extending DcR1's inhibitory action beyond the cell expressing it. This dual cell-autonomous and microenvironmental decoy mechanism is considered a contributing factor in tumor resistance to TRAIL-based therapeutic strategies.

使用情報

Application

WB, IF

Dilution

WB	IF
1:1000	1:100-1:250

Reactivity

Human

Source

Rabbit Monoclonal Antibody

MW

27 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

プロトコール

References

https://pubmed.ncbi.nlm.nih.gov/16980609/
https://pubmed.ncbi.nlm.nih.gov/9242611/

DcR1 Antibody (Rabbit mAb) [G21E20]

生物学的記述

使用情報

References

Application Data