Author response: Ki-67 is a PP1-interacting protein that organises the mitotic chromosome periphery

When the nucleolus disassembles during open mitosis, many nucleolar proteins and RNAs associate with chromosomes, establishing a perichromosomal compartment coating the chromosome periphery. At present nothing is known about the function of this poorly characterised compartment. In this study, we report that the nucleolar protein Ki-67 is required for the assembly of the perichromosomal compartment in human cells. Ki-67 is a cell-cycle regulated protein phosphatase 1-binding protein that is involved in phospho-regulation of the nucleolar protein B23/nucleophosmin. Following siRNA depletion of Ki-67, NIFK, B23, nucleolin, and four novel chromosome periphery proteins all fail to associate with the periphery of human chromosomes. Correlative light and electron microscopy (CLEM) images suggest a near-complete loss of the entire perichromosomal compartment. Mitotic chromosome condensation and intrinsic structure appear normal in the absence of the perichromosomal compartment but significant differences in nucleolar reassembly and nuclear organisation are observed in post-mitotic cells.

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The Ki-67 and RepoMan mitotic phosphatases assemble via an identical, yet novel mechanism

eLife ◽

10.7554/elife.16539 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 31

Author(s):

Ganesan Senthil Kumar ◽

Ezgi Gokhan ◽

Sofie De Munter ◽

Mathieu Bollen ◽

Paola Vagnarelli ◽

...

Keyword(s):

Protein Phosphatase ◽

Mitotic Chromosome ◽

Cancer Therapeutics ◽

Mitotic Exit ◽

Protein Phosphatase 1 ◽

Aurora B ◽

Aurora B Kinase ◽

Ki 67 ◽

Anaphase Onset

Ki-67 and RepoMan have key roles during mitotic exit. Previously, we showed that Ki-67 organizes the mitotic chromosome periphery and recruits protein phosphatase 1 (PP1) to chromatin at anaphase onset, in a similar manner as RepoMan (<xref ref-type="bibr" rid="bib2">Booth et al., 2014</xref>). Here we show how Ki-67 and RepoMan form mitotic exit phosphatases by recruiting PP1, how they distinguish between distinct PP1 isoforms and how the assembly of these two holoenzymes are dynamically regulated by Aurora B kinase during mitosis. Unexpectedly, our data also reveal that Ki-67 and RepoMan bind PP1 using an identical, yet novel mechanism, interacting with a PP1 pocket that is engaged only by these two PP1 regulators. These findings not only show how two distinct mitotic exit phosphatases are recruited to their substrates, but also provide immediate opportunities for the design of novel cancer therapeutics that selectively target the Ki-67:PP1 and RepoMan:PP1 holoenzymes.

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Low Aryl Hydrocarbon Receptor-Interacting Protein Expression Is a Better Marker of Invasiveness in Somatotropinomas than Ki-67 and p53

Neuroendocrinology ◽

10.1159/000322787 ◽

2011 ◽

Vol 94 (1) ◽

pp. 39-48 ◽

Cited By ~ 50

Author(s):

Leandro Kasuki Jomori de Pinho ◽

Leonardo Vieira Neto ◽

Luiz Eduardo Armondi Wildemberg ◽

Emerson Leandro Gasparetto ◽

Jorge Marcondes ◽

...

Keyword(s):

Protein Expression ◽

Aryl Hydrocarbon Receptor ◽

Ki 67 ◽

Interacting Protein ◽

Aryl Hydrocarbon

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Author response: Axial contraction and short-range compaction of chromatin synergistically promote mitotic chromosome condensation

10.7554/elife.10396.014 ◽

2015 ◽

Author(s):

Tom Kruitwagen ◽

Annina Denoth-Lippuner ◽

Bryan J Wilkins ◽

Heinz Neumann ◽

Yves Barral

Keyword(s):

Short Range ◽

Mitotic Chromosome ◽

Chromosome Condensation ◽

Author Response ◽

Mitotic Chromosome Condensation

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Chromosome clustering in mitosis by the nuclear protein Ki-67

Biochemical Society Transactions ◽

10.1042/bst20210717 ◽

2021 ◽

Author(s):

Konstantinos Stamatiou ◽

Paola Vagnarelli

Keyword(s):

Protein Phosphatase ◽

Mitotic Chromosome ◽

Nuclear Protein ◽

Protein A ◽

Mitotic Exit ◽

Proliferating Cells ◽

Ki 67 ◽

Mitotic Entry ◽

Long Time

Ki-67 is highly expressed in proliferating cells, a characteristic that made the protein a very important proliferation marker widely used in the clinic. However, the molecular functions and properties of Ki-67 remained quite obscure for a long time. Only recently important discoveries have shed some light on its function and shown that Ki-67 has a major role in the formation of mitotic chromosome periphery compartment, it is associated with protein phosphatase one (PP1) and regulates chromatin function in interphase and mitosis. In this review, we discuss the role of Ki-67 during cell division. Specifically, we focus on the importance of Ki-67 in chromosome individualisation at mitotic entry (prometaphase) and its contribution to chromosome clustering and nuclear remodelling during mitotic exit.

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The intrinsically disorderly story of Ki-67

Open Biology ◽

10.1098/rsob.210120 ◽

2021 ◽

Vol 11 (8) ◽

pp. 210120

Author(s):

Lucy Remnant ◽

Natalia Y. Kochanova ◽

Caitlin Reid ◽

Fernanda Cisneros-Soberanis ◽

William C. Earnshaw

Keyword(s):

Mitotic Chromosome ◽

Clinical Importance ◽

Molecular Function ◽

Proliferating Cells ◽

Ki 67 ◽

Intrinsically Disordered ◽

Disordered Structure ◽

Nucleolar Proteins ◽

Marker Proteins ◽

Liquid Liquid Phase Separation

Ki-67 is one of the most famous marker proteins used by histologists to identify proliferating cells. Indeed, over 30 000 articles referring to Ki-67 are listed on PubMed. Here, we review some of the current literature regarding the protein. Despite its clinical importance, our knowledge of the molecular biology and biochemistry of Ki-67 is far from complete, and its exact molecular function(s) remain enigmatic. Furthermore, reports describing Ki-67 function are often contradictory, and it has only recently become clear that this proliferation marker is itself dispensable for cell proliferation. We discuss the unusual organization of the protein and its mRNA and how they relate to various models for its function. In particular, we focus on ways in which the intrinsically disordered structure of Ki-67 might aid in the assembly of the still-mysterious mitotic chromosome periphery compartment by controlling liquid–liquid phase separation of nucleolar proteins and RNAs.

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