Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1

D P Harkin; J M Bean; D Miklos; Y H Song; V B Truong; C Englert; F C Christians; L W Ellisen; S Maheswaran; J D Oliner; D A Haber; Denis Harkin

Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1

D P Harkin, J M Bean, D Miklos, Y H Song, V B Truong, C Englert, F C Christians, L W Ellisen, S Maheswaran, J D Oliner, D A Haber, Denis Harkin

Research output: Contribution to journal › Article › peer-review

497 Citations (Scopus)

Abstract

The breast cancer susceptibility gene BRCA1 encodes a protein implicated in the cellular response to DNA damage, with postulated roles in homologous recombination as well as transcriptional regulation. To identify downstream target genes, we established cell lines with tightly regulated inducible expression of BRCA1. High-density oligonucleotide arrays were used to analyze gene expression profiles at various times following BRCA1 induction. A major BRCA1 target is the DNA damage-responsive gene GADD45. Induction of BRCA1 triggers apoptosis through activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), a signaling pathway potentially linked to GADD45 gene family members. The p53-independent induction of GADD45 by BRCA1 and its activation of JNK/SAPK suggest a pathway for BRCA1-induced apoptosis.

Original language	English
Pages (from-to)	575-86
Number of pages	12
Journal	Cell
Volume	97
Issue number	5
Publication status	Published - 28 May 1999

Keywords

Apoptosis
BRCA1 Protein
Breast Neoplasms
Calcium-Calmodulin-Dependent Protein Kinases
DNA Damage
Enzyme Activation
Enzyme Induction
Female
Gene Expression Regulation, Neoplastic
Gene Library
Genes, BRCA1
Humans
Intracellular Signaling Peptides and Proteins
JNK Mitogen-Activated Protein Kinases
Male
Mitogen-Activated Protein Kinases
Osteosarcoma
Protein Biosynthesis
Protein Kinases
Proteins
Signal Transduction
Testis
Tumor Cells, Cultured

UN SDGs

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title = "Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1",

abstract = "The breast cancer susceptibility gene BRCA1 encodes a protein implicated in the cellular response to DNA damage, with postulated roles in homologous recombination as well as transcriptional regulation. To identify downstream target genes, we established cell lines with tightly regulated inducible expression of BRCA1. High-density oligonucleotide arrays were used to analyze gene expression profiles at various times following BRCA1 induction. A major BRCA1 target is the DNA damage-responsive gene GADD45. Induction of BRCA1 triggers apoptosis through activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), a signaling pathway potentially linked to GADD45 gene family members. The p53-independent induction of GADD45 by BRCA1 and its activation of JNK/SAPK suggest a pathway for BRCA1-induced apoptosis.",

keywords = "Apoptosis, BRCA1 Protein, Breast Neoplasms, Calcium-Calmodulin-Dependent Protein Kinases, DNA Damage, Enzyme Activation, Enzyme Induction, Female, Gene Expression Regulation, Neoplastic, Gene Library, Genes, BRCA1, Humans, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Male, Mitogen-Activated Protein Kinases, Osteosarcoma, Protein Biosynthesis, Protein Kinases, Proteins, Signal Transduction, Testis, Tumor Cells, Cultured",

author = "Harkin, {D P} and Bean, {J M} and D Miklos and Song, {Y H} and Truong, {V B} and C Englert and Christians, {F C} and Ellisen, {L W} and S Maheswaran and Oliner, {J D} and Haber, {D A} and Denis Harkin",

year = "1999",

month = may,

day = "28",

language = "English",

volume = "97",

pages = "575--86",

journal = "Cell",

issn = "0092-8674",

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TY - JOUR

T1 - Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1

AU - Harkin, D P

AU - Bean, J M

AU - Miklos, D

AU - Song, Y H

AU - Truong, V B

AU - Englert, C

AU - Christians, F C

AU - Ellisen, L W

AU - Maheswaran, S

AU - Oliner, J D

AU - Haber, D A

AU - Harkin, Denis

PY - 1999/5/28

Y1 - 1999/5/28

N2 - The breast cancer susceptibility gene BRCA1 encodes a protein implicated in the cellular response to DNA damage, with postulated roles in homologous recombination as well as transcriptional regulation. To identify downstream target genes, we established cell lines with tightly regulated inducible expression of BRCA1. High-density oligonucleotide arrays were used to analyze gene expression profiles at various times following BRCA1 induction. A major BRCA1 target is the DNA damage-responsive gene GADD45. Induction of BRCA1 triggers apoptosis through activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), a signaling pathway potentially linked to GADD45 gene family members. The p53-independent induction of GADD45 by BRCA1 and its activation of JNK/SAPK suggest a pathway for BRCA1-induced apoptosis.

AB - The breast cancer susceptibility gene BRCA1 encodes a protein implicated in the cellular response to DNA damage, with postulated roles in homologous recombination as well as transcriptional regulation. To identify downstream target genes, we established cell lines with tightly regulated inducible expression of BRCA1. High-density oligonucleotide arrays were used to analyze gene expression profiles at various times following BRCA1 induction. A major BRCA1 target is the DNA damage-responsive gene GADD45. Induction of BRCA1 triggers apoptosis through activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), a signaling pathway potentially linked to GADD45 gene family members. The p53-independent induction of GADD45 by BRCA1 and its activation of JNK/SAPK suggest a pathway for BRCA1-induced apoptosis.

KW - Apoptosis

KW - BRCA1 Protein

KW - Breast Neoplasms

KW - Calcium-Calmodulin-Dependent Protein Kinases

KW - DNA Damage

KW - Enzyme Activation

KW - Enzyme Induction

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Gene Library

KW - Genes, BRCA1

KW - Humans

KW - Intracellular Signaling Peptides and Proteins

KW - JNK Mitogen-Activated Protein Kinases

KW - Male

KW - Mitogen-Activated Protein Kinases

KW - Osteosarcoma

KW - Protein Biosynthesis

KW - Protein Kinases

KW - Proteins

KW - Signal Transduction

KW - Testis

KW - Tumor Cells, Cultured

M3 - Article

C2 - 10367887

VL - 97

SP - 575

EP - 586

JO - Cell

JF - Cell

SN - 0092-8674

IS - 5

ER -

Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1

Abstract

Keywords

UN SDGs

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