JMJD5 (Jumonji Domain-containing 5) Associates with Spindle Microtubules and Is Required for Proper Mitosis

He, Zhong; Wu, Junyu; Su, Xuantao; Zhang, Ye; Pan, Lixia; Wei, Huimin; Fang, Qiang; Li, Haitao; Wang, Da-Liang; Sun, Fang-Lin

doi:10.1074/jbc.m115.672642

Cited by 20 publications

(27 citation statements)

References 47 publications

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“…17 In a previous study, we demonstrated that JMJD5 regulated the stability of the mitotic spindle and played an important role in mitosis. 33 In the present study, we evaluated the function of cytoplasmic JMJD5. We found that JMJD5 modulated the stability of cytoskeletal microtubules by regulating MAP1B protein levels and that JMJD5 depletion significantly increased the sensitivity of cancer cells to microtubule-destabilizing agents.…”

Section: Discussionmentioning

confidence: 99%

“…33 To determine if JMJD5 regulates the stability of cytoplasmic microtubules, we evaluated cells transfected with 2 distinct siRNAs targeting JMJD5. As shown in Fig.…”

Section: Jmjd5 Depletion Significantly Reduces A-tubulin Acetylation mentioning

confidence: 99%

“…The rabbit anti-JMJD5 antibody was generated by Abmart. 33 The antibody against detyrosinated-a-tubulin was obtained from Millipore. Antibodies against MAP1B, MAP1S, PARP and Bcl-2 were purchased from Proteintech, and the antibody against H1 was obtained from Bioworld.…”

Section: Reagents and Antibodiesmentioning

confidence: 99%

“…33 The GFP-MAP1B plasmid was a gift from Phillip Gordon-Weeks (Addgene plasmid # 44396). 50 The control siRNA (5 0 -UUCUCCGAACGUGUCACGUTT-3 0 ) and siJMJD5-2 (5 0 -CCAGAUGUGAAGUUAGAAATT-3 0 ) were synthesized by GenePharma (Shanghai, China), and siJMJD5-1 (sc-75359) was purchased from Santa Cruz Biotechnology.…”

Section: Plasmids and Sirnasmentioning

confidence: 99%

“…[23][24][25][26][27][28][29][30][31][32] In addition, we previously reported that JMJD5 associated with the mitotic spindle and regulated mitotic spindle stability during mitosis. 33 However, it remains unclear about the functional role of JMJD5 in regulating cytoskeletal microtubule stability and its molecular mechanism.…”

Section: Introductionmentioning

confidence: 99%

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Depletion of JMJD5 sensitizes tumor cells to microtubule-destabilizing agents by altering microtubule stability

Wang

et al. 2016

Cell Cycle

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Microtubules play essential roles in mitosis, cell migration, and intracellular trafficking. Drugs that target microtubules have demonstrated great clinical success in cancer treatment due to their capacity to impair microtubule dynamics in both mitotic and interphase stages. In a previous report, we demonstrated that JMJD5 associated with mitotic spindle and was required for proper mitosis. However, it remains elusive whether JMJD5 could regulate the stability of cytoskeletal microtubules and whether it affects the efficacy of microtubuletargeting agents. In this study, we find that JMJD5 localizes not only to the nucleus, a fraction of it also localizes to the cytoplasm. JMJD5 depletion decreases the acetylation and detyrosination of a-tubulin, both of which are markers of microtubule stability. In addition, microtubules in JMJD5-depleted cells are more sensitive to nocodazole-induced depolymerization, whereas JMJD5 overexpression increases a-tubulin detyrosination and enhances the resistance of microtubules to nocodazole. Mechanistic studies revealed that JMJD5 regulates MAP1B protein levels and that MAP1B overexpression rescued the microtubule destabilization induced by JMJD5 depletion. Furthermore, JMJD5 depletion significantly promoted apoptosis in cancer cells treated with the microtubule-targeting anti-cancer drugs vinblastine or colchicine. Together, these findings suggest that JMJD5 is required to regulate the stability of cytoskeletal microtubules and that JMJD5 depletion increases the susceptibility of cancer cells to microtubule-destabilizing agents.

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Section: Discussionmentioning

confidence: 99%

“…33 To determine if JMJD5 regulates the stability of cytoplasmic microtubules, we evaluated cells transfected with 2 distinct siRNAs targeting JMJD5. As shown in Fig.…”

Section: Jmjd5 Depletion Significantly Reduces A-tubulin Acetylation mentioning

confidence: 99%

Section: Reagents and Antibodiesmentioning

confidence: 99%

Section: Plasmids and Sirnasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Depletion of JMJD5 sensitizes tumor cells to microtubule-destabilizing agents by altering microtubule stability

Wang

et al. 2016

Cell Cycle

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Histone lysine demethylases and their functions in cancer

Sterling

Menezes

Abbassi

et al. 2020

Intl Journal of Cancer

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Histone lysine demethylases (KDMs) are enzymes that remove the methylation marks on lysines in nucleosomes' histone tails. These changes in methylation marks regulate gene transcription during both development and malignant transformation. Depending on which lysine residue is targeted, the effect of a given KDM on gene transcription can be either activating or repressing, and KDMs can regulate the expression of both oncogenes and tumour suppressors. Thus, the functions of KDMs can be regarded as both oncogenic and tumour suppressive, contingent on cell context and the enzyme isoform. Finally, KDMs also demethylate nonhistone proteins and have a variety of demethylase‐independent functions. These epigenetic and other mechanisms that KDMs control make them important regulators of malignant tumours. Here, we present an overview of eight KDM subfamilies, their most‐studied lysine targets and selected recent data on their roles in cancer stem cells, tumour aggressiveness and drug tolerance.

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Microtubules: From understanding their dynamics to using them as potential therapeutic targets

Ilan

2018

Journal Cellular Physiology

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Microtubules (MT) and actin microfilaments are dynamic cytoskeleton components involved in a range of intracellular processes. MTs play a role in cell division, beating of cilia and flagella, and intracellular transport. Over the past decades, much knowledge has been gained regarding MT function and structure, and its role in underlying disease progression. This makes MT potential therapeutic targets for various disorders. Disturbances in MT and their associated proteins are the underlying cause of diseases such as Alzheimer’s disease, cancer, and several genetic diseases. Some of the advances in the field of MT research, as well as the potenti G beta gamma, is needed al uses of MT‐targeting agents in various conditions have been reviewed here.

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JMJD5 (Jumonji Domain-containing 5) Associates with Spindle Microtubules and Is Required for Proper Mitosis

Cited by 20 publications

References 47 publications

Depletion of JMJD5 sensitizes tumor cells to microtubule-destabilizing agents by altering microtubule stability

Depletion of JMJD5 sensitizes tumor cells to microtubule-destabilizing agents by altering microtubule stability

Histone lysine demethylases and their functions in cancer

Microtubules: From understanding their dynamics to using them as potential therapeutic targets

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