The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family

a potential role in the regulation of higher-order chromatin structure

Thomas Scholzen, Elmar Endl, Claudia Wohlenberg, Sjaak van der Sar, Ian G Cowell, Johannes Gerdes, Prim B Singh

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

The expression of the nuclear protein Ki-67 (pKi-67) is strictly correlated with cell proliferation. Because of this, anti-Ki-67 antibodies can be used as operational markers to estimate the growth fraction of human neoplasia in situ. For a variety of tumours, the assessment of pKi-67 expression has repeatedly been proven to be of prognostic value for survival and tumour recurrence, but no cellular function has yet been ascribed to the Ki-67 protein. This study shows that a C-terminal domain of pKi-67 (Kon21) is able to bind to all three members of the mammalian heterochromatin protein 1 (HP1) family in vitro and in vivo. This interaction can be manipulated in living cells, as evidenced by ectopic expression of GFP-tagged HP1 proteins in HeLa cells, which results in a dramatic relocalization of endogenous pKi-67. Taken together, the data presented in this study suggest a role for pKi-67 in the control of higher-order chromatin structure.

Original languageEnglish
Pages (from-to)135-44
Number of pages10
JournalJournal of Pathology
Volume196
Issue number2
DOIs
Publication statusPublished - Feb 2002

Fingerprint

Chromatin
Proteins
Neoplasms
Nuclear Proteins
HeLa Cells
Cell Proliferation
heterochromatin-specific nonhistone chromosomal protein HP-1
Recurrence
Survival
Antibodies
Growth

Keywords

  • Animals
  • Cell Division
  • Cell Nucleus
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Fluorescent Antibody Technique
  • Green Fluorescent Proteins
  • HeLa Cells
  • Humans
  • Interphase
  • Ki-67 Antigen
  • Luminescent Proteins
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Transfection
  • Two-Hybrid System Techniques
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family : a potential role in the regulation of higher-order chromatin structure. / Scholzen, Thomas; Endl, Elmar; Wohlenberg, Claudia; van der Sar, Sjaak; Cowell, Ian G; Gerdes, Johannes; Singh, Prim B.

In: Journal of Pathology, Vol. 196, No. 2, 02.2002, p. 135-44.

Research output: Contribution to journalArticle

Scholzen, Thomas ; Endl, Elmar ; Wohlenberg, Claudia ; van der Sar, Sjaak ; Cowell, Ian G ; Gerdes, Johannes ; Singh, Prim B. / The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family : a potential role in the regulation of higher-order chromatin structure. In: Journal of Pathology. 2002 ; Vol. 196, No. 2. pp. 135-44.
@article{1643c0ba4e2c447fbda2aa78a62bdf65,
title = "The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family: a potential role in the regulation of higher-order chromatin structure",
abstract = "The expression of the nuclear protein Ki-67 (pKi-67) is strictly correlated with cell proliferation. Because of this, anti-Ki-67 antibodies can be used as operational markers to estimate the growth fraction of human neoplasia in situ. For a variety of tumours, the assessment of pKi-67 expression has repeatedly been proven to be of prognostic value for survival and tumour recurrence, but no cellular function has yet been ascribed to the Ki-67 protein. This study shows that a C-terminal domain of pKi-67 (Kon21) is able to bind to all three members of the mammalian heterochromatin protein 1 (HP1) family in vitro and in vivo. This interaction can be manipulated in living cells, as evidenced by ectopic expression of GFP-tagged HP1 proteins in HeLa cells, which results in a dramatic relocalization of endogenous pKi-67. Taken together, the data presented in this study suggest a role for pKi-67 in the control of higher-order chromatin structure.",
keywords = "Animals, Cell Division, Cell Nucleus, Chromatin, Chromosomal Proteins, Non-Histone, Fluorescent Antibody Technique, Green Fluorescent Proteins, HeLa Cells, Humans, Interphase, Ki-67 Antigen, Luminescent Proteins, Protein Isoforms, Recombinant Fusion Proteins, Transfection, Two-Hybrid System Techniques, Journal Article, Research Support, Non-U.S. Gov't",
author = "Thomas Scholzen and Elmar Endl and Claudia Wohlenberg and {van der Sar}, Sjaak and Cowell, {Ian G} and Johannes Gerdes and Singh, {Prim B}",
note = "Copyright 2001 John Wiley & Sons, Ltd.",
year = "2002",
month = "2",
doi = "10.1002/path.1016",
language = "English",
volume = "196",
pages = "135--44",
journal = "Journal of Pathology",
issn = "0022-3417",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

TY - JOUR

T1 - The Ki-67 protein interacts with members of the heterochromatin protein 1 (HP1) family

T2 - a potential role in the regulation of higher-order chromatin structure

AU - Scholzen, Thomas

AU - Endl, Elmar

AU - Wohlenberg, Claudia

AU - van der Sar, Sjaak

AU - Cowell, Ian G

AU - Gerdes, Johannes

AU - Singh, Prim B

N1 - Copyright 2001 John Wiley & Sons, Ltd.

PY - 2002/2

Y1 - 2002/2

N2 - The expression of the nuclear protein Ki-67 (pKi-67) is strictly correlated with cell proliferation. Because of this, anti-Ki-67 antibodies can be used as operational markers to estimate the growth fraction of human neoplasia in situ. For a variety of tumours, the assessment of pKi-67 expression has repeatedly been proven to be of prognostic value for survival and tumour recurrence, but no cellular function has yet been ascribed to the Ki-67 protein. This study shows that a C-terminal domain of pKi-67 (Kon21) is able to bind to all three members of the mammalian heterochromatin protein 1 (HP1) family in vitro and in vivo. This interaction can be manipulated in living cells, as evidenced by ectopic expression of GFP-tagged HP1 proteins in HeLa cells, which results in a dramatic relocalization of endogenous pKi-67. Taken together, the data presented in this study suggest a role for pKi-67 in the control of higher-order chromatin structure.

AB - The expression of the nuclear protein Ki-67 (pKi-67) is strictly correlated with cell proliferation. Because of this, anti-Ki-67 antibodies can be used as operational markers to estimate the growth fraction of human neoplasia in situ. For a variety of tumours, the assessment of pKi-67 expression has repeatedly been proven to be of prognostic value for survival and tumour recurrence, but no cellular function has yet been ascribed to the Ki-67 protein. This study shows that a C-terminal domain of pKi-67 (Kon21) is able to bind to all three members of the mammalian heterochromatin protein 1 (HP1) family in vitro and in vivo. This interaction can be manipulated in living cells, as evidenced by ectopic expression of GFP-tagged HP1 proteins in HeLa cells, which results in a dramatic relocalization of endogenous pKi-67. Taken together, the data presented in this study suggest a role for pKi-67 in the control of higher-order chromatin structure.

KW - Animals

KW - Cell Division

KW - Cell Nucleus

KW - Chromatin

KW - Chromosomal Proteins, Non-Histone

KW - Fluorescent Antibody Technique

KW - Green Fluorescent Proteins

KW - HeLa Cells

KW - Humans

KW - Interphase

KW - Ki-67 Antigen

KW - Luminescent Proteins

KW - Protein Isoforms

KW - Recombinant Fusion Proteins

KW - Transfection

KW - Two-Hybrid System Techniques

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/path.1016

DO - 10.1002/path.1016

M3 - Article

VL - 196

SP - 135

EP - 144

JO - Journal of Pathology

JF - Journal of Pathology

SN - 0022-3417

IS - 2

ER -