WD repeat-containing protein 5 (WDR5) localizes to the midbody and regulates abscission.

Bailey, Jeffrey K; Fields, Alexander T.; Cheng, Kaijian; Lee, Albert; Wagenaar, Eric; Lagrois, Remy; Schmidt, Bailey; Xia, Bin; Ma, Dzwokai

doi:10.1074/jbc.a114.623611

Cited by 9 publications

(10 citation statements)

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“…We not only found N and C subunits of MLL on the spindle apparatus, but also WDR5 and RbBP5, components of the MLL core complex. In support of our findings, the Drosophila trithorax and WDS (will die slowly), ortholog of mammalian MLL and WDR5, respectively, as well as human WDR5, have been identified as associated with microtubules in different studies (Hughes et al, 2008;Sauer et al, 2005;Bailey et al, 2015). Various other chromatin modifiers have been shown to localize to the non-chromatin subcellular structures during mitosis to serve transcription-independent functions.…”

Section: Mll Complex Emerges As a Major Regulator Of Mitosissupporting

confidence: 84%

MLL/WDR5 Complex Regulates Kif2A Localization to Ensure Chromosome Congression and Proper Spindle Assembly during Mitosis

et al. 2017

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Mixed-lineage leukemia (MLL), along with multisubunit (WDR5, RbBP5, ASH2L, and DPY30) complex catalyzes the trimethylation of H3K4, leading to gene activation. Here, we characterize a chromatin-independent role for MLL during mitosis. MLL and WDR5 localize to the mitotic spindle apparatus, and loss of function of MLL complex by RNAi results in defects in chromosome congression and compromised spindle formation. We report interaction of MLL complex with several kinesin and dynein motors. We further show that the MLL complex associates with Kif2A, a member of the Kinesin-13 family of microtubule depolymerase, and regulates the spindle localization of Kif2A during mitosis. We have identified a conserved WDR5 interaction (Win) motif, so far unique to the MLL family, in Kif2A. The Win motif of Kif2A engages in direct interactions with WDR5 for its spindle localization. Our findings highlight a non-canonical mitotic function of MLL complex, which may have a direct impact on chromosomal stability, frequently compromised in cancer.

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Section: Mll Complex Emerges As a Major Regulator Of Mitosissupporting

confidence: 84%

MLL/WDR5 Complex Regulates Kif2A Localization to Ensure Chromosome Congression and Proper Spindle Assembly during Mitosis

et al. 2017

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“…Interestingly, the Drosophila trithorax, ortholog of mammalian MLL, was identified as microtubule-associated proteins (MAPs) in large scale proteomic analysis [37]. Other members of MLL complex like WDR5 and RbBP5 have been reported on microtubule-rich structures before [17,[37][38][39] and a large number of mitotic proteins associate with them [17,38,40]. The localizations reported here indicate towards potential novel undiscovered roles of MLL in mitosis.…”

Section: Novel Localization Of Mll In Mitosismentioning

confidence: 69%

Novel sub-cellular localizations and intra-molecular interactions may define new functions of Mixed Lineage Leukemia protein

et al. 2018

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Mixed-lineage leukemia (MLL) protein is the best-characterized member of SET family of histone 3 lysine 4 methyltransferase, known for its transcriptional-activation role during development. mll gene rearrangements cause multiple kinds of aggressive leukemia in both children and adults. An important 'first' step in understanding the role of MLL in leukemogenesis would be to identify its localization throughout the cell cycle. In order to fully understand the breath of MLL functions in proliferating cells, we have analyzed its sub-cellular localization during the cell cycle. Our results show that MLL localizes to nucleolus and centrosome in interphase. During mitosis, it localizes to centrosomes and midbody in addition to previously reported spindle apparatus. Our results show that MLL N is required to translocate MLL C to the nucleolus. These finding suggest functional roles for MLL in nucleolus and mitosis. We also show how MLL-fusion proteins (MLL-FPs) localize to the same sub-cellular organelles like endogenous MLL. Our results indicate that MLL-fusion proteins may not only disturb the cell homeostasis by gain-of-function of the chimeric protein, but also by interfering with the functions of endogenous MLL. ARTICLE HISTORY

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“…Midbodies were isolated from HeLa cells as described previously [48,49]. Briefly, HeLa cells were collected after synchronized by thymidine/nocodazole followed by mitotic shake-off.…”

Section: Midbody Isolationmentioning

confidence: 99%

Nucleoporin Nup58 localizes to centrosomes and mid-bodies during mitosis

et al. 2019

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Background: Nuclear pore complexes (NPCs) act as nano-turnstiles within nuclear membranes between the cytoplasm and nucleus of mammalian cells. NPC proteins, called nucleoporins (Nups), mediate trafficking of proteins and RNA into and out of the nucleus, and are involved in a variety of mitotic processes. We previously reported that Nup62 localizes to the centrosome and mitotic spindle during mitosis, and plays a role in centrosome homeostasis. However, whether Nup58, a Nup62 subcomplex protein, also localizes to spindle poles is unknown. Result: Herein, we show that Nup58 localizes to the nuclear rim during interphase, and to mitotic spindles, centrosomes, and midbodies during mitosis. Our confocal microscopy, live-cell imaging, and stimulated emission depletion nanoscopy results also demonstrated that Nup58 localized to the centrosomes during metaphase and relocalized to midbodies during abscission. Depletion of Nup58 resulted in centrosomal abnormalities and delayed abscission. Conclusion: Nup58 localized at the centrosomes and mitotic spindle during metaphase and relocalized at midbodies during abscission. This study highlights the important role of Nup58 in mitosis.

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WD repeat-containing protein 5 (WDR5) localizes to the midbody and regulates abscission.

Abstract: Authors are urged to introduce these corrections into any reprints they distribute. Secondary (abstract) services are urged to carry notice of these corrections as prominently as they carried the original abstracts.

Cited by 9 publications

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MLL/WDR5 Complex Regulates Kif2A Localization to Ensure Chromosome Congression and Proper Spindle Assembly during Mitosis

MLL/WDR5 Complex Regulates Kif2A Localization to Ensure Chromosome Congression and Proper Spindle Assembly during Mitosis

Novel sub-cellular localizations and intra-molecular interactions may define new functions of Mixed Lineage Leukemia protein

Nucleoporin Nup58 localizes to centrosomes and mid-bodies during mitosis

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