The inhibitor of growth protein 5 (ING5) depends on INCA1 as a co-factor for its antiproliferative effects

Feng Zhang, Nicole Bäumer, Miriam Rode, Ping Ji, Tao Zhang, Wolfgang E. Berdel, Carsten Müller-Tidow

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The proteins of the Inhibitor of Growth (ING) family are involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. For ING5, its actual role in growth suppression and the necessary partners are not known. In a yeast-two-hybrid approach with human bone marrow derived cDNA, we identified ING5 as well as several other proteins as interaction partners of Inhibitor of cyclin A1 (INCA1) that we previously characterized as a novel interaction partner of cyclin A1/CDK2. ING5 expression in leukemic AML blasts was severely reduced compared to normal bone marrow. In line, ING5 inhibited bone marrow colony formation upon retroviral transduction. However, Inca1-/- bone marrow colony formation was not suppressed by ING5. In murine embryonic fibroblast (MEF) cells from Inca1+/+ and Inca1-/- mice, overexpression of ING5 suppressed cell proliferation only in the presence of INCA1, while ING5 had no effect in Inca1-/- MEFs. ING5 overexpression induced a delay in S-phase progression, which required INCA1. Finally, ING5 overexpression enhanced Fas-induced apoptosis in Inca1+/+ MEFs, while Inca1-/- MEFs were protected from Fas antibody-induced apoptosis. Taken together, these results indicate that ING5 is a growth suppressor with suppressed expression in AML whose functions depend on its interaction with INCA1.

Original languageEnglish (US)
Article numbere21505
JournalPLoS One
Volume6
Issue number7
DOIs
StatePublished - 2011
Externally publishedYes

Fingerprint

Cyclin A1
Growth Inhibitors
cyclins
Proteins
proteins
bone marrow
Bone
Bone Marrow
apoptosis
Apoptosis
Cells
Chromatin Assembly and Disassembly
mice
Cell proliferation
Fibroblasts
Growth

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The inhibitor of growth protein 5 (ING5) depends on INCA1 as a co-factor for its antiproliferative effects. / Zhang, Feng; Bäumer, Nicole; Rode, Miriam; Ji, Ping; Zhang, Tao; Berdel, Wolfgang E.; Müller-Tidow, Carsten.

In: PLoS One, Vol. 6, No. 7, e21505, 2011.

Research output: Contribution to journalArticle

Zhang, Feng ; Bäumer, Nicole ; Rode, Miriam ; Ji, Ping ; Zhang, Tao ; Berdel, Wolfgang E. ; Müller-Tidow, Carsten. / The inhibitor of growth protein 5 (ING5) depends on INCA1 as a co-factor for its antiproliferative effects. In: PLoS One. 2011 ; Vol. 6, No. 7.
@article{37b0a75b1d0b4f45919c25cb97fd5090,
title = "The inhibitor of growth protein 5 (ING5) depends on INCA1 as a co-factor for its antiproliferative effects",
abstract = "The proteins of the Inhibitor of Growth (ING) family are involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. For ING5, its actual role in growth suppression and the necessary partners are not known. In a yeast-two-hybrid approach with human bone marrow derived cDNA, we identified ING5 as well as several other proteins as interaction partners of Inhibitor of cyclin A1 (INCA1) that we previously characterized as a novel interaction partner of cyclin A1/CDK2. ING5 expression in leukemic AML blasts was severely reduced compared to normal bone marrow. In line, ING5 inhibited bone marrow colony formation upon retroviral transduction. However, Inca1-/- bone marrow colony formation was not suppressed by ING5. In murine embryonic fibroblast (MEF) cells from Inca1+/+ and Inca1-/- mice, overexpression of ING5 suppressed cell proliferation only in the presence of INCA1, while ING5 had no effect in Inca1-/- MEFs. ING5 overexpression induced a delay in S-phase progression, which required INCA1. Finally, ING5 overexpression enhanced Fas-induced apoptosis in Inca1+/+ MEFs, while Inca1-/- MEFs were protected from Fas antibody-induced apoptosis. Taken together, these results indicate that ING5 is a growth suppressor with suppressed expression in AML whose functions depend on its interaction with INCA1.",
author = "Feng Zhang and Nicole B{\"a}umer and Miriam Rode and Ping Ji and Tao Zhang and Berdel, {Wolfgang E.} and Carsten M{\"u}ller-Tidow",
year = "2011",
doi = "10.1371/journal.pone.0021505",
language = "English (US)",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - The inhibitor of growth protein 5 (ING5) depends on INCA1 as a co-factor for its antiproliferative effects

AU - Zhang, Feng

AU - Bäumer, Nicole

AU - Rode, Miriam

AU - Ji, Ping

AU - Zhang, Tao

AU - Berdel, Wolfgang E.

AU - Müller-Tidow, Carsten

PY - 2011

Y1 - 2011

N2 - The proteins of the Inhibitor of Growth (ING) family are involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. For ING5, its actual role in growth suppression and the necessary partners are not known. In a yeast-two-hybrid approach with human bone marrow derived cDNA, we identified ING5 as well as several other proteins as interaction partners of Inhibitor of cyclin A1 (INCA1) that we previously characterized as a novel interaction partner of cyclin A1/CDK2. ING5 expression in leukemic AML blasts was severely reduced compared to normal bone marrow. In line, ING5 inhibited bone marrow colony formation upon retroviral transduction. However, Inca1-/- bone marrow colony formation was not suppressed by ING5. In murine embryonic fibroblast (MEF) cells from Inca1+/+ and Inca1-/- mice, overexpression of ING5 suppressed cell proliferation only in the presence of INCA1, while ING5 had no effect in Inca1-/- MEFs. ING5 overexpression induced a delay in S-phase progression, which required INCA1. Finally, ING5 overexpression enhanced Fas-induced apoptosis in Inca1+/+ MEFs, while Inca1-/- MEFs were protected from Fas antibody-induced apoptosis. Taken together, these results indicate that ING5 is a growth suppressor with suppressed expression in AML whose functions depend on its interaction with INCA1.

AB - The proteins of the Inhibitor of Growth (ING) family are involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. For ING5, its actual role in growth suppression and the necessary partners are not known. In a yeast-two-hybrid approach with human bone marrow derived cDNA, we identified ING5 as well as several other proteins as interaction partners of Inhibitor of cyclin A1 (INCA1) that we previously characterized as a novel interaction partner of cyclin A1/CDK2. ING5 expression in leukemic AML blasts was severely reduced compared to normal bone marrow. In line, ING5 inhibited bone marrow colony formation upon retroviral transduction. However, Inca1-/- bone marrow colony formation was not suppressed by ING5. In murine embryonic fibroblast (MEF) cells from Inca1+/+ and Inca1-/- mice, overexpression of ING5 suppressed cell proliferation only in the presence of INCA1, while ING5 had no effect in Inca1-/- MEFs. ING5 overexpression induced a delay in S-phase progression, which required INCA1. Finally, ING5 overexpression enhanced Fas-induced apoptosis in Inca1+/+ MEFs, while Inca1-/- MEFs were protected from Fas antibody-induced apoptosis. Taken together, these results indicate that ING5 is a growth suppressor with suppressed expression in AML whose functions depend on its interaction with INCA1.

UR - http://www.scopus.com/inward/record.url?scp=79960014273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960014273&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0021505

DO - 10.1371/journal.pone.0021505

M3 - Article

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e21505

ER -