O-glycans on death receptors in cells modulate their sensitivity to TRAIL-induced apoptosis through affecting on their stability and oligomerization.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Yuliang JiangTongzhong Ju

Abstract

The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex. Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive. Normal extended O-glycan biosynthesis is regulated by a specific molecular chaperone Cosmc through assisting of the correct folding of Core 1 β3 Galactosyltransferase (T-synthase). Here, we use tumor cell lines harboring mutations in Cosmc, and therefore expressing Tn and STn antigens to study the role of O-glycans in TRAIL-induced apoptosis. Expression of Tn and STn in tumor cells attenuates their sensitivity to TRAIL treatment; when transfected with wild-type Cosmc, these tumor cells thus express normal extended O-glycans and become more sensitive to TRAIL treatment. Mechanistically, Tn/STn antigens impair homo-oligomerization and stability of DR4 and DR5. These results represent the first mechanistic...Continue Reading

References

Nov 1, 1992·The Journal of Cell Biology·Y GavrieliS A Ben-Sasson
Mar 1, 1990·Gynecologic Oncology·M SuzukiT Tamada
Sep 1, 1971·The Journal of Pathology·J F Kerr
Jun 15, 1984·Science·G F Springer
May 1, 1995·British Journal of Cancer·S A Brooks, A J Leathem
Dec 1, 1996·Pathology, Research and Practice·R SoaresF Schmitt
Jul 20, 1999·The Journal of Clinical Investigation·A AshkenaziR H Schwall
Dec 14, 1999·Nature Structural Biology·J MongkolsapayaG R Screaton
Dec 2, 1999·Biochimica Et Biophysica Acta·I Brockhausen
Mar 31, 2000·Experimental Cell Research·H Walczak, P H Krammer
Oct 24, 2001·The Journal of Biological Chemistry·Tongzhong JuWilliam M Canfield
Oct 26, 2001·The Journal of Biological Chemistry·Tongzhong JuWilliam M Canfield
Feb 8, 2002·Cell·Ricky W JohnstoneScott W Lowe
Dec 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tongzhong Ju, Richard D Cummings
Feb 1, 2003·Cancer Cell·John C Reed
Nov 25, 2003·Oncogene·Shulin Wang, Wafik S El-Deiry
Jan 28, 2004·The Journal of Cell Biology·Lijun XiaRodger P McEver
Aug 4, 2004·Cellular and Molecular Life Sciences : CMLS·P SecchieroG Zauli
Oct 28, 2005·Nature·Tongzhong Ju, Richard D Cummings
Dec 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Lauren ClancyFrancis Ka-Ming Chan
Apr 12, 2006·Carcinogenesis·Boris Zhivotovsky, Sten Orrenius
Oct 14, 2006·Science·Andrea SchietingerHans Schreiber
Apr 18, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Carmelo Carlo-StellaLuca Gianni
Sep 4, 2007·Nature Chemical Biology·Sampat IngaleGeert-Jan Boons
Mar 15, 2008·Cancer Research·Tongzhong JuRichard D Cummings
Apr 1, 2008·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Andrew ThorburnHeide Ford
Jun 10, 2008·British Journal of Haematology·Vanja Karamatic CrewDavid J Anstee
Aug 13, 2008·The Journal of Cell Biology·Tongzhong JuRichard D Cummings
Sep 25, 2008·Nature Reviews. Cancer·Ricky W JohnstoneMark J Smyth
Sep 3, 2009·Chemical Communications : Chem Comm·Therese BuskasGeert-Jan Boons

❮ Previous
Next ❯

Citations

Oct 23, 2020·Nature Reviews. Molecular Cell Biology·Katrine T SchjoldagerHenrik Clausen
Mar 2, 2021·Frontiers in Cell and Developmental Biology·Kirstin Kucka, Harald Wajant
Mar 23, 2021·Journal of Biochemistry·Kenta MoriwakiEiji Miyoshi
Jul 20, 2021·Cellular and Molecular Life Sciences : CMLS·Elham KhosrowabadiSakari Kellokumpu
Oct 7, 2021·Science Advances·Junwei ZengRichard D Cummings

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis