Cell cycle–regulated membrane binding of NuMA contributes to efficient anaphase chromosome separation

Zheng, Zongheng; Wan, Qingwen; Meixiong, Gerry; Du, Quansheng

doi:10.1091/mbc.e13-08-0474

Cited by 49 publications

(86 citation statements)

References 64 publications

(102 reference statements)

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“…Although elucidation of regulation of its function remains in progress, it is clear that, during mitosis, CDK1-dependent phosphorylation causes NuMA to concentrate at spindle poles and to induce a redistribution of dynein that results in chromosome segregation and eventually the division of the nucleus (Lelievre et al, 1998;Abad et al, 2007;Kotak et al, 2013;Zheng et al, 2014). Data in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In proliferating cells, mitosis requires cyclin-dependent kinase 1 (CDK1) in conjunction with cyclins A or B to phosphorylate nuclear membrane lamins to destabilize the nuclear envelope (reviewed by Nigg, 1993). Activated CDK1 also aids in regulating mitotic chromatin (reviewed by Nigg, 1993;Kotak et al, 2013;Orthwein et al, 2014;Zheng et al, 2014). By contrast, post-mitotic cells rarely exhibit CDK1 and cyclin A/B expression (King et al, 1994;Tommasi and Pfeifer, 1995).…”

Section: Introductionmentioning

confidence: 99%

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Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly

et al. 2014

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Lens epithelial cells and early lens fiber cells contain the typical complement of intracellular organelles. However, as lens fiber cells mature they must destroy their organelles, including nuclei, in a process that has remained enigmatic for over a century, but which is crucial for the formation of the organelle-free zone in the center of the lens that assures clarity and function to transmit light. Nuclear degradation in lens fiber cells requires the nuclease DNase IIβ (DLAD) but the mechanism by which DLAD gains access to nuclear DNA remains unknown. In eukaryotic cells, cyclin-dependent kinase 1 (CDK1), in combination with either activator cyclins A or B, stimulates mitotic entry, in part, by phosphorylating the nuclear lamin proteins leading to the disassembly of the nuclear lamina and subsequent nuclear envelope breakdown. Although most post-mitotic cells lack CDK1 and cyclins, lens fiber cells maintain these proteins. Here, we show that loss of CDK1 from the lens inhibited the phosphorylation of nuclear lamins A and C, prevented the entry of DLAD into the nucleus, and resulted in abnormal retention of nuclei. In the presence of CDK1, a single focus of the phosphonuclear mitotic apparatus is observed, but it is not focused in CDK1-deficient lenses. CDK1 deficiency inhibited mitosis, but did not prevent DNA replication, resulting in an overall reduction of lens epithelial cells, with the remaining cells possessing an abnormally large nucleus. These observations suggest that CDK1-dependent phosphorylations required for the initiation of nuclear membrane disassembly during mitosis are adapted for removal of nuclei during fiber cell differentiation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly

et al. 2014

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“…Indeed, although CDK1 phosphorylates NuMA at the C-terminus in vertebrate cells, this step is not thought to affect interaction with dynein. Rather, phosphorylation acts as a temporal switch for activity; at anaphase, dephosphorylation allows NuMA to bind the membrane directly, where it associates with dynein to anchor the spindle poles at opposite sides as the cell elongates and divides (Kiyomitsu and Cheeseman, 2013;Kotak et al, 2013;Seldin et al, 2013;Zheng et al, 2014). In Drosophila, the kinase Warts is reported to phosphorylate Mud to promote association with Pins (Dewey et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Spindle orientation: a question of complex positioning

2017

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The direction in which a cell divides is determined by the orientation of its mitotic spindle at metaphase. Spindle orientation is therefore important for a wide range of developmental processes, ranging from germline stem cell division to epithelial tissue homeostasis and regeneration. In multiple cell types in multiple animals, spindle orientation is controlled by a conserved biological machine that mediates a pulling force on astral microtubules. Restricting the localization of this machine to only specific regions of the cortex can thus determine how the mitotic spindle is oriented. As we review here, recent findings based on studies in tunicate, worm, fly and vertebrate cells have revealed that the mechanisms for mediating this restriction are surprisingly diverse.

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“…2) [57]. It plays an essential role in spindle pole organization during mitosis [58] and is present in the chromatin compartment of the nucleus to control cell fate, chromatin organization, and DNA damage responses [59]. …”

Section: Introductionmentioning

confidence: 99%

Molecular Characteristics and Clinical Significance of 12 Fusion Genes in Acute Promyelocytic Leukemia: A Systematic Review

Yan

Zhang²

2016

Acta Haematol

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Acute promyelocytic leukemia (APL) is characterized by the generation of the promyelocytic leukemia-retinoic acid (RA) receptor α (PML-RARα) fusion gene. PML-RARα is the central leukemia-initiating event in APL and is directly targeted by all-trans-RA (ATRA) as well as arsenic. In classic APL harboring PML-RARα transcripts, more than 90% of patients can achieve complete remission when treated with ATRA combined with arsenic trioxide chemotherapy. In the last 20 years, more than 10 variant fusion genes have been found and identified in APL patients. These variant APL cases present different clinical phenotypes and treatment outcomes. All variant APL cases show a similar breakpoint within the RARα gene, whereas its partner genes are variable. These fusion proteins have the ability to repress rather than activate retinoic targets. These chimeric proteins also possess different molecular characteristics, thereby resulting in variable sensitivities to ATRA and clinical outcomes. In this review, we comprehensively analyze various rearrangements in variant APL cases that have been reported in the literature as well as the molecular characteristics and functions of the fusion proteins derived from different RARα partner genes and their clinical implications.

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Cell cycle–regulated membrane binding of NuMA contributes to efficient anaphase chromosome separation

Abstract: The mitotic apparatus protein NuMA has an intrinsic membrane-targeting mechanism that is regulated by CDK1-mediated phosphorylation, underlies anaphase-specific cortical accumulation of dynein, and contributes to chromosome separation.

Cited by 49 publications

References 64 publications

Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly

Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly

Spindle orientation: a question of complex positioning

Molecular Characteristics and Clinical Significance of 12 Fusion Genes in Acute Promyelocytic Leukemia: A Systematic Review

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