Regulation in the targeting of TRAIL receptor 1 to cell surface via GODZ for TRAIL sensitivity in tumor cells

Yumin Oh, Y. J. Jeon, G. S. Hong, I. Kim, H. N. Woo, Y. K. Jung

Research output: Contribution to journalArticle

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5), promote the selective clearing of various malignancies by inducing apoptosis, holding the promise as a potent therapeutic agent for anticancer. Though DR4 and DR5 have high sequence similarity, differential regulation of both receptors in human tumor cells remains largely unexplored. Here, we repot that golgi-specific Asp-His-His-Cys (DHHC) zinc finger protein (GODZ) regulates TRAIL/DR4-mediated apoptosis. Using the SOS protein recruitment-yeast two-hybrid screening, we isolated GODZ that interacted with the death domain of DR4. GODZ binds to DR4, but not to DR5, through the DHHC and the C-terminal transmembrane domain. Expression level of GODZ affects apoptosis of tumor cells triggered by TRAIL, but not that induced by TNF-a/cycloheximide (CHX) or DNA-damaging drugs. In parallel, GODZ functions to localize DR4 to the plasma membrane (PM) via DHHC motif. Also, introduction of mutation into the cysteine-rich motif of DR4 results in its mistargeting and attenuates TRAIL-or GODZ-mediated apoptosis. Interestingly, GODZ expression is highly downregulated in Hep-3B tumor cells, which show resistance to TRAIL. However, reconstitution of GODZ expression enhances the targeting of DR4 to cell surface and sensitizes Hep-3B cells to TRAIL. Taken together, these data establish that GODZ is a novel DR4-selective regulator responsible for targeting of DR4 to the PM, and thereby for TRAIL-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)1196-1207
Number of pages12
JournalCell Death and Differentiation
Volume19
Issue number7
DOIs
StatePublished - Jul 2012
Externally publishedYes

Fingerprint

TNF-Related Apoptosis-Inducing Ligand Receptors
Apoptosis
Neoplasms
Drosophila Son of Sevenless Protein
Cell Membrane
Zinc Fingers
Cycloheximide
Antineoplastic Agents
Cysteine
Down-Regulation
Tumor Necrosis Factor-alpha
Yeasts
Ligands
Mutation
DNA
Pharmaceutical Preparations

Keywords

  • cell surface
  • DR4
  • GODZ
  • targeting
  • TRAIL

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Regulation in the targeting of TRAIL receptor 1 to cell surface via GODZ for TRAIL sensitivity in tumor cells. / Oh, Yumin; Jeon, Y. J.; Hong, G. S.; Kim, I.; Woo, H. N.; Jung, Y. K.

In: Cell Death and Differentiation, Vol. 19, No. 7, 07.2012, p. 1196-1207.

Research output: Contribution to journalArticle

Oh, Yumin ; Jeon, Y. J. ; Hong, G. S. ; Kim, I. ; Woo, H. N. ; Jung, Y. K. / Regulation in the targeting of TRAIL receptor 1 to cell surface via GODZ for TRAIL sensitivity in tumor cells. In: Cell Death and Differentiation. 2012 ; Vol. 19, No. 7. pp. 1196-1207.
@article{149c323f070f478eaac344d6f71075cb,
title = "Regulation in the targeting of TRAIL receptor 1 to cell surface via GODZ for TRAIL sensitivity in tumor cells",
abstract = "Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5), promote the selective clearing of various malignancies by inducing apoptosis, holding the promise as a potent therapeutic agent for anticancer. Though DR4 and DR5 have high sequence similarity, differential regulation of both receptors in human tumor cells remains largely unexplored. Here, we repot that golgi-specific Asp-His-His-Cys (DHHC) zinc finger protein (GODZ) regulates TRAIL/DR4-mediated apoptosis. Using the SOS protein recruitment-yeast two-hybrid screening, we isolated GODZ that interacted with the death domain of DR4. GODZ binds to DR4, but not to DR5, through the DHHC and the C-terminal transmembrane domain. Expression level of GODZ affects apoptosis of tumor cells triggered by TRAIL, but not that induced by TNF-a/cycloheximide (CHX) or DNA-damaging drugs. In parallel, GODZ functions to localize DR4 to the plasma membrane (PM) via DHHC motif. Also, introduction of mutation into the cysteine-rich motif of DR4 results in its mistargeting and attenuates TRAIL-or GODZ-mediated apoptosis. Interestingly, GODZ expression is highly downregulated in Hep-3B tumor cells, which show resistance to TRAIL. However, reconstitution of GODZ expression enhances the targeting of DR4 to cell surface and sensitizes Hep-3B cells to TRAIL. Taken together, these data establish that GODZ is a novel DR4-selective regulator responsible for targeting of DR4 to the PM, and thereby for TRAIL-induced apoptosis.",
keywords = "cell surface, DR4, GODZ, targeting, TRAIL",
author = "Yumin Oh and Jeon, {Y. J.} and Hong, {G. S.} and I. Kim and Woo, {H. N.} and Jung, {Y. K.}",
year = "2012",
month = "7",
doi = "10.1038/cdd.2011.209",
language = "English (US)",
volume = "19",
pages = "1196--1207",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Regulation in the targeting of TRAIL receptor 1 to cell surface via GODZ for TRAIL sensitivity in tumor cells

AU - Oh, Yumin

AU - Jeon, Y. J.

AU - Hong, G. S.

AU - Kim, I.

AU - Woo, H. N.

AU - Jung, Y. K.

PY - 2012/7

Y1 - 2012/7

N2 - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5), promote the selective clearing of various malignancies by inducing apoptosis, holding the promise as a potent therapeutic agent for anticancer. Though DR4 and DR5 have high sequence similarity, differential regulation of both receptors in human tumor cells remains largely unexplored. Here, we repot that golgi-specific Asp-His-His-Cys (DHHC) zinc finger protein (GODZ) regulates TRAIL/DR4-mediated apoptosis. Using the SOS protein recruitment-yeast two-hybrid screening, we isolated GODZ that interacted with the death domain of DR4. GODZ binds to DR4, but not to DR5, through the DHHC and the C-terminal transmembrane domain. Expression level of GODZ affects apoptosis of tumor cells triggered by TRAIL, but not that induced by TNF-a/cycloheximide (CHX) or DNA-damaging drugs. In parallel, GODZ functions to localize DR4 to the plasma membrane (PM) via DHHC motif. Also, introduction of mutation into the cysteine-rich motif of DR4 results in its mistargeting and attenuates TRAIL-or GODZ-mediated apoptosis. Interestingly, GODZ expression is highly downregulated in Hep-3B tumor cells, which show resistance to TRAIL. However, reconstitution of GODZ expression enhances the targeting of DR4 to cell surface and sensitizes Hep-3B cells to TRAIL. Taken together, these data establish that GODZ is a novel DR4-selective regulator responsible for targeting of DR4 to the PM, and thereby for TRAIL-induced apoptosis.

AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5), promote the selective clearing of various malignancies by inducing apoptosis, holding the promise as a potent therapeutic agent for anticancer. Though DR4 and DR5 have high sequence similarity, differential regulation of both receptors in human tumor cells remains largely unexplored. Here, we repot that golgi-specific Asp-His-His-Cys (DHHC) zinc finger protein (GODZ) regulates TRAIL/DR4-mediated apoptosis. Using the SOS protein recruitment-yeast two-hybrid screening, we isolated GODZ that interacted with the death domain of DR4. GODZ binds to DR4, but not to DR5, through the DHHC and the C-terminal transmembrane domain. Expression level of GODZ affects apoptosis of tumor cells triggered by TRAIL, but not that induced by TNF-a/cycloheximide (CHX) or DNA-damaging drugs. In parallel, GODZ functions to localize DR4 to the plasma membrane (PM) via DHHC motif. Also, introduction of mutation into the cysteine-rich motif of DR4 results in its mistargeting and attenuates TRAIL-or GODZ-mediated apoptosis. Interestingly, GODZ expression is highly downregulated in Hep-3B tumor cells, which show resistance to TRAIL. However, reconstitution of GODZ expression enhances the targeting of DR4 to cell surface and sensitizes Hep-3B cells to TRAIL. Taken together, these data establish that GODZ is a novel DR4-selective regulator responsible for targeting of DR4 to the PM, and thereby for TRAIL-induced apoptosis.

KW - cell surface

KW - DR4

KW - GODZ

KW - targeting

KW - TRAIL

UR - http://www.scopus.com/inward/record.url?scp=84862128939&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862128939&partnerID=8YFLogxK

U2 - 10.1038/cdd.2011.209

DO - 10.1038/cdd.2011.209

M3 - Article

C2 - 22240897

AN - SCOPUS:84862128939

VL - 19

SP - 1196

EP - 1207

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

IS - 7

ER -