Dynamic phosphorylation of HP1α regulates mitotic progression in human cells

Chakraborty, Arindam; Prasanth, Kannanganattu V.; Prasanth, Supriya G.

doi:10.1038/ncomms4445

Cited by 32 publications

(41 citation statements)

References 69 publications

(103 reference statements)

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“…We have recently shown that mammalian NDR kinases phosphorylate HP1α during G 2 /M phase, and that this phosphorylation is crucial for mitotic progression. 27 In this "Extra Views" article we have further dissected the role of hinge-phosphorylated HP1α during the progression through mitosis. Our results suggest that dephosphorylation of hinge-phosphorylated HP1α begins at prometaphase, continues progressively through mitosis, and culminates by the end of mitosis, and this is necessary for the successful mitotic exit in mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation–dephosphorylation cycle of HP1α governs accurate mitotic progression

Chakraborty¹,

Prasanth

2014

Cell Cycle

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H eterochromatin protein 1α (HP1α), a bona fide factor of silent chromatin, is required for establishing as well as maintaining the higher-order chromatin structure in eukaryotes. HP1α is decorated with several post-translational modifications, and many of these are critical for its cellular functions. HP1α is heavily phosphorylated; however, its physiological relevance had remained to be completely understood. We have recently demonstrated that human HP1α is a mitotic target for NDR kinase, and the phosphorylation at the hinge region of HP1α at the G 2 /M phase of the cell cycle is crucial for mitotic progression and Sgo1 loading at mitotic centromeres (Chakraborty et al., 2014). We now demonstrate that the dephosphorylation of HP1α within its hinge domain occurs during mitosis, specifically soon after prometaphase. In the absence of the hinge-specific HP1α phosphorylation, either as a consequence of depleting NDR1 or in cells expressing a non-phosphorylatable HP1α mutant, the cells arrest in prometaphase with several mitotic defects. In this study we show that NDR1-depleted cells expressing hinge-specific phosphomimetic HP1α mutant rescues the prometaphase arrest but displays defects in mitotic exit, suggesting that the dephosphorylation of HP1α is required for the completion of cytokinesis. Taken together, our results reveal that the phosphorylation-dephosphorylation cycle of HP1α orchestrates accurate progression of cells through mitosis.

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Section: Introductionmentioning

confidence: 99%

Phosphorylation–dephosphorylation cycle of HP1α governs accurate mitotic progression

Chakraborty¹,

Prasanth

2014

Cell Cycle

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“…Altogether this points to the interconnection between HP1a post-translational modifications and accurate chromosome alignment during mitotic progression. 84,85 In this line the functional interaction between HP1 and BRCA1 also might be interesting.…”

Section: How Epigenetics Control Exerted By Hp1a Can Influence the Onmentioning

confidence: 91%

“…83 A direct link between acquired HP1a post-translational modifications and the HP1a mitotic functions was recently described. 84,85 Whereas HP1a is constitutively phosphorylated at the N-terminal region, the hinge domain is preferentially phosphorylated at G2/M phase of the cell cycle. This hinge domain phosphorylated form of HP1a is specifically localized to kinetochores during early mitosis.…”

Section: How Epigenetics Control Exerted By Hp1a Can Influence the Onmentioning

confidence: 99%

“…This hinge domain phosphorylated form of HP1a is specifically localized to kinetochores during early mitosis. 84,85 HP1a hinge domain phosphorylation is mediated by NDR1 kinase and is required for mitotic progression and SGO1 binding to mitotic centromeres. 84,85 Cells lacking NDR kinase exhibit a loss of mitosis specific HP1a phosphorylation followed by prometaphase arrest.…”

Section: How Epigenetics Control Exerted By Hp1a Can Influence the Onmentioning

confidence: 99%

“…84,85 HP1a hinge domain phosphorylation is mediated by NDR1 kinase and is required for mitotic progression and SGO1 binding to mitotic centromeres. 84,85 Cells lacking NDR kinase exhibit a loss of mitosis specific HP1a phosphorylation followed by prometaphase arrest. Altogether this points to the interconnection between HP1a post-translational modifications and accurate chromosome alignment during mitotic progression.…”

Section: How Epigenetics Control Exerted By Hp1a Can Influence the Onmentioning

confidence: 99%

See 2 more Smart Citations

Beyond the histone tale: HP1α deregulation in breast cancer epigenetics

Vad-Nielsen

Nielsen

2015

Cancer Biology & Therapy

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H eterochromatin protein 1a (HP1a) encoded from the CBX5-gene is an evolutionary conserved protein that binds histone H3 di-or tri-methylated at position lysine 9 (H3K9me2/3), a hallmark for heterochromatin, and has an essential role in forming higher order chromatin structures. HP1a has diverse functions in heterochromatin formation, gene regulation, and mitotic progression, and forms complex networks of gene, RNA, and protein interactions. Emerging evidence has shown that HP1a serves a unique biological role in breast cancer related processes and in particular for epigenetic control mechanisms involved in aberrant cell proliferation and metastasis. However, how HP1a deregulation plays dual mechanistic functions for cancer cell proliferation and metastasis suppression and the underlying cellular mechanisms are not yet comprehensively described. In this paper we provide an overview of the role of HP1a as a new sight of epigenetics in proliferation and metastasis of human breast cancer. This highlights the importance of addressing HP1a in breast cancer diagnostics and therapeutics.

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Functions of HP1 in preventing chromosomal instability

Ding,

Peng,

Zeng

et al. 2024

Cell Biochemistry & Function

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Chromosomal instability (CIN), caused by errors in the segregation of chromosomes during mitosis, is a hallmark of many types of cancer. The fidelity of chromosome segregation is governed by a sophisticated cellular signaling network, one crucial orchestrator of which is Heterochromatin protein 1 (HP1). HP1 dynamically localizes to distinct sites at various stages of mitosis, where it regulates key mitotic events ranging from chromosome–microtubule attachment to sister chromatid cohesion to cytokinesis. Our evolving comprehension of HP1's multifaceted role has positioned it as a central protein in the orchestration of mitotic processes.

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Dynamic phosphorylation of HP1α regulates mitotic progression in human cells

Cited by 32 publications

References 69 publications

Phosphorylation–dephosphorylation cycle of HP1α governs accurate mitotic progression

Phosphorylation–dephosphorylation cycle of HP1α governs accurate mitotic progression

Beyond the histone tale: HP1α deregulation in breast cancer epigenetics

Functions of HP1 in preventing chromosomal instability

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