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

doi:10.1002/path.1016

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

Department of Medicine

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

82 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 language	English
Pages (from-to)	135-44
Number of pages	10
Journal	Journal of Pathology
Volume	196
Issue number	2
DOIs	https://doi.org/10.1002/path.1016
Publication status	Published - Feb 2002

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

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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 journal › Article › peer-review

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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}",

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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.

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