DR5 (Fc-Fusion)

Similar to DR4, expression of DR5 is quite broad. Unlike DR4, for which three distinct transcripts can be detected, only one transcript of 4.4 kb was detected. Similar to DR4, DR5 has an unusually long signal peptide (51 amino acids), a CRD domain and a death domain that are most closely related to DR4.

Interacting protein(s): TRAIL (P7008F)
Related products: TNF-Receptor Superfamily

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Description

DR5, also known as TRAIL-R2, was identified from EST data by two groups through searching for homologs of the TNFR1 death domain or the DR4 cysteine-rich domain (CRD). Two variants were found, one with an insertion of membrane proximal TAPE motif. Similar to DR4, expression of DR5 is quite broad. Unlike DR4, for which three distinct transcripts can be detected, only one transcript of 4.4 kb was detected. Similar to DR4, DR5 has an unusually long signal peptide (51 amino acids), a CRD domain and a death domain that are most closely related to DR4.

Overexpression of DR5 in 293T cells also trigger the rounding up and the morphological changes typical of apoptosis. While DR5 is capable of triggering apoptosis, it is controversial whether the signalling pathway involved its association with FADD and whether it is capable of activating NfκB.

It is likely that unique cell types and properties may contribute to these differences. Interestingly, DR4 and DR5 appear to be functional redundant and their expression profiles are not sufficiently different to suggest a distinct tissue involvement of TRIAL signalling. Nonetheless, these they may have additional, non-redundant signalling functions, perhaps mediated by structure outside of the closely related death domain.

Amino Acid Sequence.

References

1. Gampa SC, Garimella SV, Pandrangi S. Nano-TRAIL: a promising path to cancer therapy. Cancer Drug Resist. 2023;6(1):78-102. Epub 20230201. doi: 10.20517/cdr.2022.82. PubMed PMID: 37065863; PubMed Central PMCID: PMC10099604.

2. Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, et al. (1997) Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277:818-821.

3. Schneider P, Bodmer JL, Thome M, Hofmann K, Holler N, Tschopp J. (1997) Characterization of two receptors for TRAIL. FEBS Lett. 416:329-334.

4. Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM. (1997) An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277:815-818.

5. Schneider P, Thome M, Burns K, Bodmer JL, Hofmann K, Kataoka T, Holler N, Tschopp J. (1997) TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB. Immunity. 7:831-836.