Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy

Research output: Contribution to journalJournal article – Annual report year: 2015Researchpeer-review

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Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy. / So, Jonathan; Pasculescu, Adrian; Dai, Anna Y.; Williton, Kelly; James, Andrew; Nguyen, Vivian; Creixell, Pau; Schoof, Erwin M.; Sinclair, John; Barrios-Rodiles, Miriam; Gu, Jun; Krizus, Aldis; Williams, Ryan; Olhovsky, Marina; Dennis, James W.; Wrana, Jeffrey L.; Linding, Rune; Jørgensen, Claus; Pawson, Tony; Colwill, Karen.

In: Science Signaling, Vol. 8, No. 371, rs3, 2015.

Research output: Contribution to journalJournal article – Annual report year: 2015Researchpeer-review

Harvard

So, J, Pasculescu, A, Dai, AY, Williton, K, James, A, Nguyen, V, Creixell, P, Schoof, EM, Sinclair, J, Barrios-Rodiles, M, Gu, J, Krizus, A, Williams, R, Olhovsky, M, Dennis, JW, Wrana, JL, Linding, R, Jørgensen, C, Pawson, T & Colwill, K 2015, 'Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy', Science Signaling, vol. 8, no. 371, rs3. https://doi.org/10.1126/scisignal.2005700

APA

CBE

So J, Pasculescu A, Dai AY, Williton K, James A, Nguyen V, Creixell P, Schoof EM, Sinclair J, Barrios-Rodiles M, Gu J, Krizus A, Williams R, Olhovsky M, Dennis JW, Wrana JL, Linding R, Jørgensen C, Pawson T, Colwill K. 2015. Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy. Science Signaling. 8(371). https://doi.org/10.1126/scisignal.2005700

MLA

Vancouver

Author

So, Jonathan ; Pasculescu, Adrian ; Dai, Anna Y. ; Williton, Kelly ; James, Andrew ; Nguyen, Vivian ; Creixell, Pau ; Schoof, Erwin M. ; Sinclair, John ; Barrios-Rodiles, Miriam ; Gu, Jun ; Krizus, Aldis ; Williams, Ryan ; Olhovsky, Marina ; Dennis, James W. ; Wrana, Jeffrey L. ; Linding, Rune ; Jørgensen, Claus ; Pawson, Tony ; Colwill, Karen. / Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy. In: Science Signaling. 2015 ; Vol. 8, No. 371.

Bibtex

@article{880eb304a3ba44f497c30ea23dde98a7,
title = "Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy",
abstract = "Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous secreted peptide and, in preclinical studies, preferentially induces apoptosis in tumor cells rather than in normal cells. The acquisition of resistance in cells exposed to TRAIL or its mimics limits their clinical efficacy. Because kinases are intimately involved in the regulation of apoptosis, we systematically characterized kinases involved in TRAIL signaling. Using RNA interference (RNAi) loss-of-function and cDNA overexpression screens, we identified 169 protein kinases that influenced the dynamics of TRAIL-induced apoptosis in the colon adenocarcinoma cell line DLD-1. We classified the kinases as sensitizers or resistors or modulators, depending on the effect that knockdown and overexpression had on TRAIL-induced apoptosis. Two of these kinases that were classified as resistors were PX domain-containing serine/threonine kinase (PXK) and AP2-associated kinase 1 (AAK1), which promote receptor endocytosis and may enable cells to resist TRAIL-induced apoptosis by enhancing endocytosis of the TRAIL receptors. We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative phosphoproteomics. With these protein interaction maps, we modeled information flow through the networks and identified apoptosis-modifying kinases that are highly connected to regulated substrates downstream of TRAIL. The results of this analysis provide a resource of potential targets for the development of TRAIL combination therapies to selectively kill cancer cells.",
keywords = "apoptosis, cancer Neoplasms (MeSH) neoplastic disease, Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] DLD-1 cell line cell_line human colon adenocarcinoma cells, AAK1, cDNA complementary DNA expression, protein kinase 372092-80-3 EC 2.7.13.3, PXK, TRAIL receptor, TRAIL signaling, 02508, Cytology - Human, 10060, Biochemistry studies - General, 10062, Biochemistry studies - Nucleic acids, purines and pyrimidines, 10802, Enzymes - General and comparative studies: coenzymes, 12512, Pathology - Therapy, 22002, Pharmacology - General, 22005, Pharmacology - Clinical pharmacology, 24004, Neoplasms - Pathology, clinical aspects and systemic effects, combination therapy therapeutic and prophylactic techniques, clinical techniques, mass spectrometry-based protein interaction analysis laboratory techniques, spectrum analysis techniques, RNA interference RNAi laboratory techniques, genetic techniques, Biochemistry and Molecular Biophysics, Pharmacology, Tumor Biology, BIOCHEMISTRY, CELL, NF-KAPPA-B, DEPENDENT PROTEIN-KINASE, INTEGRIN-LINKED KINASE, CASPASE RECRUITMENT DOMAIN, HIGHLY OPTIMIZED TOLERANCE, LIGAND-INDUCED APOPTOSIS, LIGHT-INDUCED APOPTOSIS, ALPHA-INDUCED APOPTOSIS, CELL-CYCLE ARREST, CANCER-CELLS, Research Resources, Systems Biology",
author = "Jonathan So and Adrian Pasculescu and Dai, {Anna Y.} and Kelly Williton and Andrew James and Vivian Nguyen and Pau Creixell and Schoof, {Erwin M.} and John Sinclair and Miriam Barrios-Rodiles and Jun Gu and Aldis Krizus and Ryan Williams and Marina Olhovsky and Dennis, {James W.} and Wrana, {Jeffrey L.} and Rune Linding and Claus J{\o}rgensen and Tony Pawson and Karen Colwill",
year = "2015",
doi = "10.1126/scisignal.2005700",
language = "English",
volume = "8",
journal = "Science Signaling",
issn = "1945-0877",
publisher = "American Association for the Advancement of Science",
number = "371",

}

RIS

TY - JOUR

T1 - Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy

AU - So, Jonathan

AU - Pasculescu, Adrian

AU - Dai, Anna Y.

AU - Williton, Kelly

AU - James, Andrew

AU - Nguyen, Vivian

AU - Creixell, Pau

AU - Schoof, Erwin M.

AU - Sinclair, John

AU - Barrios-Rodiles, Miriam

AU - Gu, Jun

AU - Krizus, Aldis

AU - Williams, Ryan

AU - Olhovsky, Marina

AU - Dennis, James W.

AU - Wrana, Jeffrey L.

AU - Linding, Rune

AU - Jørgensen, Claus

AU - Pawson, Tony

AU - Colwill, Karen

PY - 2015

Y1 - 2015

N2 - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous secreted peptide and, in preclinical studies, preferentially induces apoptosis in tumor cells rather than in normal cells. The acquisition of resistance in cells exposed to TRAIL or its mimics limits their clinical efficacy. Because kinases are intimately involved in the regulation of apoptosis, we systematically characterized kinases involved in TRAIL signaling. Using RNA interference (RNAi) loss-of-function and cDNA overexpression screens, we identified 169 protein kinases that influenced the dynamics of TRAIL-induced apoptosis in the colon adenocarcinoma cell line DLD-1. We classified the kinases as sensitizers or resistors or modulators, depending on the effect that knockdown and overexpression had on TRAIL-induced apoptosis. Two of these kinases that were classified as resistors were PX domain-containing serine/threonine kinase (PXK) and AP2-associated kinase 1 (AAK1), which promote receptor endocytosis and may enable cells to resist TRAIL-induced apoptosis by enhancing endocytosis of the TRAIL receptors. We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative phosphoproteomics. With these protein interaction maps, we modeled information flow through the networks and identified apoptosis-modifying kinases that are highly connected to regulated substrates downstream of TRAIL. The results of this analysis provide a resource of potential targets for the development of TRAIL combination therapies to selectively kill cancer cells.

AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous secreted peptide and, in preclinical studies, preferentially induces apoptosis in tumor cells rather than in normal cells. The acquisition of resistance in cells exposed to TRAIL or its mimics limits their clinical efficacy. Because kinases are intimately involved in the regulation of apoptosis, we systematically characterized kinases involved in TRAIL signaling. Using RNA interference (RNAi) loss-of-function and cDNA overexpression screens, we identified 169 protein kinases that influenced the dynamics of TRAIL-induced apoptosis in the colon adenocarcinoma cell line DLD-1. We classified the kinases as sensitizers or resistors or modulators, depending on the effect that knockdown and overexpression had on TRAIL-induced apoptosis. Two of these kinases that were classified as resistors were PX domain-containing serine/threonine kinase (PXK) and AP2-associated kinase 1 (AAK1), which promote receptor endocytosis and may enable cells to resist TRAIL-induced apoptosis by enhancing endocytosis of the TRAIL receptors. We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative phosphoproteomics. With these protein interaction maps, we modeled information flow through the networks and identified apoptosis-modifying kinases that are highly connected to regulated substrates downstream of TRAIL. The results of this analysis provide a resource of potential targets for the development of TRAIL combination therapies to selectively kill cancer cells.

KW - apoptosis

KW - cancer Neoplasms (MeSH) neoplastic disease

KW - Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] DLD-1 cell line cell_line human colon adenocarcinoma cells

KW - AAK1

KW - cDNA complementary DNA expression

KW - protein kinase 372092-80-3 EC 2.7.13.3

KW - PXK

KW - TRAIL receptor

KW - TRAIL signaling

KW - 02508, Cytology - Human

KW - 10060, Biochemistry studies - General

KW - 10062, Biochemistry studies - Nucleic acids, purines and pyrimidines

KW - 10802, Enzymes - General and comparative studies: coenzymes

KW - 12512, Pathology - Therapy

KW - 22002, Pharmacology - General

KW - 22005, Pharmacology - Clinical pharmacology

KW - 24004, Neoplasms - Pathology, clinical aspects and systemic effects

KW - combination therapy therapeutic and prophylactic techniques, clinical techniques

KW - mass spectrometry-based protein interaction analysis laboratory techniques, spectrum analysis techniques

KW - RNA interference RNAi laboratory techniques, genetic techniques

KW - Biochemistry and Molecular Biophysics

KW - Pharmacology

KW - Tumor Biology

KW - BIOCHEMISTRY

KW - CELL

KW - NF-KAPPA-B

KW - DEPENDENT PROTEIN-KINASE

KW - INTEGRIN-LINKED KINASE

KW - CASPASE RECRUITMENT DOMAIN

KW - HIGHLY OPTIMIZED TOLERANCE

KW - LIGAND-INDUCED APOPTOSIS

KW - LIGHT-INDUCED APOPTOSIS

KW - ALPHA-INDUCED APOPTOSIS

KW - CELL-CYCLE ARREST

KW - CANCER-CELLS

KW - Research Resources

KW - Systems Biology

U2 - 10.1126/scisignal.2005700

DO - 10.1126/scisignal.2005700

M3 - Journal article

VL - 8

JO - Science Signaling

JF - Science Signaling

SN - 1945-0877

IS - 371

M1 - rs3

ER -