Antagonistic activities of CDC14B and CDK1 on USP9X regulate WT1-dependent mitotic transcription and survival

Dietachmayr, Michael; Rathakrishnan, Abirami; Karpiuk, Oleksandra; Zweydorf, Felix von; Engleitner, Thomas; Fernández‐Sáiz, Vanesa; Schenk, Petra; Ueffing, Marius; Rad, Roland; Eilers, Martin; Gloeckner, Christian; Hohenberg, Katharina Clemm von; Bassermann, Florian

doi:10.1038/s41467-020-15059-5

Cited by 27 publications

(23 citation statements)

References 56 publications

(69 reference statements)

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“…It may indicate that METTL3 could increase the infiltration level of Th22 cell by MAPK-CCL20 signal. In addition, Wilms’ tumor protein 1(WT1) could function as a mitotic transcription factor and specify CXCL8/IL-8 as a target gene of WT1 that conveys mitotic survival 74 , while Wilms’ tumor 1-associating protein (WTAP) has been identified as a key subunit of the m6A methyltransferase complex, which indirectly identify the WTAP could regulate the MDSC infiltration to affect the immune environment.…”

Section: Introductionmentioning

confidence: 99%

Emerging role of RNA modification N6-methyladenosine in immune evasion

et al. 2021

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The innate and adaptive immune cells have complex signaling pathways for sensing and initiating immune responses against disease. These pathways are interrupted at different levels to occur immune evasion, including by N6-methyladenosine (m6A) modification. In this review, we discuss studies revealing the immune evasion mechanism by m6A modification, which underlies the retouching of these signaling networks and the rapid tolerance of innate and adaptive immune molecules during disease. We also focus on the functions of m6A in main chemokines regulation, and their roles in promotive and suppressive immune cell recruitment. We then discuss some of the current challenges in the field and describe future directions for the immunological mechanisms of m6A modification.

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Section: Introductionmentioning

confidence: 99%

Emerging role of RNA modification N6-methyladenosine in immune evasion

et al. 2021

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“…Interestingly, in addition to direct deubiquitination of TGFBR2 protein, USP9X also maintains TGFBR2 mRNA levels in GCs indirectly via the SMAD4/miR‐143 axis. These transcriptional or posttranscriptional regulatory functions of USP9X are often mediated by different substrates (Dietachmayr et al, 2020; Jie et al, 2021). In hypoxic breast cancer stem cells, for instance, USP9X interacts with HIF‐1a, leading to deubiquitination and stabilization of the latter, followed by transcription of the TERT gene by acting as a transcription factor (Lu et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

TGFBR2 is a novel substrate and indirect transcription target of deubiquitylase USP9X in granulosa cells

Yang

Wang

Pan

et al. 2022

Journal Cellular Physiology

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The ubiquitin‐specific peptidase 9 X‐linked (USP9X) is one of the highly conserved members belonging to the ubiquitin‐specific proteases (USPs) family, which has been reported to control substrates‐mediated biological functions through deubiquitinating and stabilizing substrates. Here, we have found that TGFBR2, the type II receptor of the transforming growth factor beta (TGF‐β) signaling pathway, is a novel substrate and indirect transcription target of deubiquitylase USP9X in granulosa cells (GCs). Mechanically, USP9X positively influences the expression of TGFBR2 at different levels through two independent ways: (i) directly targets and deubiquitinates TGFBR2, which maintains the protein stability of TGFBR2 through avoiding degradation mediated by ubiquitin‐proteasome system; (ii) indirectly maintains TGFBR2 messenger RNA (mRNA) expression via SMAD4/miR‐143 axis. Specifically, SMAD4, another substrate of USP9X, acts as a transcription factor and suppresses miR‐143 which inhibits the mRNA level of TGFBR2 by directly binding to its 3′‐untranslated region. Functionally, the maintenance of TGFBR2 by USP9X activates the TGF‐β signaling pathway, which further represses GC apoptosis. Our study highlights a functional micro‐regulatory network composed of deubiquitinase (USP9X), small noncoding RNA (miR‐143) and the TGF‐β signaling pathway, which plays a crucial role in the regulation of GC apoptosis and female fertility.

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“…This localization has been implicated in mitotic bookmarking, which is required to maintain transcriptional programs upon entry into G 1 (Kadauke and Blobel 2013 ; Liu et al 2017 ; Sarnataro et al 2021 ; Soares et al 2021 ; Teves et al 2016 ) . Additionally, active transcription of specific genes during mitosis is required for mitotic survival (Dietachmayr et al 2020 ). There is now growing support for a more direct role for transcription factors in mitosis-specific processes.…”

Section: Discussionmentioning

confidence: 99%

Transcription factor Sp1 regulates mitotic chromosome assembly and segregation

et al. 2022

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Aneuploidy is a pervasive feature of cancer cells that results from chromosome missegregation. Several transcription factors have been associated with aneuploidy; however, no studies to date have demonstrated that mammalian transcription factors directly regulate chromosome segregation during mitosis. Here, we demonstrate that the ubiquitously expressed transcription factor specificity protein 1 (Sp1), which we have previously linked to aneuploidy, has a mitosis-specific role regulating chromosome segregation. We find that Sp1 localizes to mitotic centromeres and auxin-induced rapid Sp1 degradation at mitotic onset results in chromosome segregation errors and aberrant mitotic progression. Furthermore, rapid Sp1 degradation results in anomalous mitotic chromosome assembly characterized by loss of condensin complex I localization to mitotic chromosomes and chromosome condensation defects. Consistent with these defects, Sp1 degradation results in reduced chromosome passenger complex activity and histone H3 serine 10 phosphorylation during mitosis, which is essential for condensin complex I recruitment and chromosome condensation. Together, these data provide the first evidence of a mammalian transcription factor acting specifically during mitosis to regulate chromosome segregation.

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Antagonistic activities of CDC14B and CDK1 on USP9X regulate WT1-dependent mitotic transcription and survival

Cited by 27 publications

References 56 publications

Emerging role of RNA modification N6-methyladenosine in immune evasion

Emerging role of RNA modification N6-methyladenosine in immune evasion

TGFBR2 is a novel substrate and indirect transcription target of deubiquitylase USP9X in granulosa cells

Transcription factor Sp1 regulates mitotic chromosome assembly and segregation

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