scholarly journals Aurora kinase A mediated phosphorylation of mPOU is critical for skeletal muscle differentiation

2019 ◽  
Author(s):  
Dhanasekaran Karthigeyan ◽  
Arnab Bose ◽  
Ramachandran Boopathi ◽  
Vinay Jaya Rao ◽  
Hiroki Shima ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Aurora Kinase ◽  
Muscle Differentiation ◽  
Negative Regulator ◽  
Myoblast Differentiation ◽  
C2c12 Myoblast ◽  
Skeletal Muscle Differentiation ◽  
Skeletal Myogenesis ◽  
Aurora Kinase A ◽  
Kinase A

AbstractAurora kinases are Ser/Thr-directed protein kinases which play pivotal roles in mitosis. Recent evidences highlight the importance of these kinases in non-mitotic biological events like skeletal myogenesis. Our earlier study identified POU6F1 (or mPOU) as a novel Aurora kinase A (AurkA) substrate. Here, we report that AurkA phosphorylates POU6F1 at Ser197 and inhibits its DNA binding ability. Delving into POU6F1 physiology, we find that the phospho-mimic (S197D) POU6F1 mutant exhibits enhancement, while wild type (WT) or phospho-deficient (S197A) mutant shows retardation in C2C12 myoblast differentiation. Interestingly, POU6F1 depletion phenocopies S197D-POU6F1 overexpression in the differentiation context. Collectively, our results signify mPOU as a negative regulator of skeletal muscle differentiation and strengthens the importance of AurkA in skeletal myogenesis.

Aurora kinase A-mediated phosphorylation of mPOU at a specific site drives skeletal muscle differentiation

2019 ◽  
Vol 167 (2) ◽  
pp. 195-201
Author(s):  
Dhanasekan Karthigeyan ◽  
Arnab Bose ◽  
Ramachandran Boopathi ◽  
Vinay Jaya Rao ◽  
Hiroki Shima ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Aurora Kinase ◽  
Muscle Differentiation ◽  
Negative Regulator ◽  
Myoblast Differentiation ◽  
C2c12 Myoblast ◽  
Skeletal Muscle Differentiation ◽  
Binding Ability ◽  
Aurora Kinase A ◽  
Kinase A

Abstract Aurora kinases are Ser/Thr-directed protein kinases which play pivotal roles in mitosis. Recent evidences highlight the importance of these kinases in multiple biological events including skeletal muscle differentiation. Our earlier study identified the transcription factor POU6F1 (or mPOU) as a novel Aurora kinase (Aurk) A substrate. Here, we report that Aurora kinase A phosphorylates mPOU at Ser197 and inhibit its DNA-binding ability. Delving into mPOU physiology, we find that the phospho-mimic (S197D) mPOU mutant exhibits enhancement, while the wild type or the phospho-deficient mutant shows retardation in C2C12 myoblast differentiation. Interestingly, POU6F1 depletion phenocopies S197D-mPOU overexpression in the differentiation context. Collectively, our results signify mPOU as a negative regulator of skeletal muscle differentiation and strengthen the importance of AurkA in skeletal myogenesis.

scholarly journals Zfp422 promotes skeletal muscle differentiation by regulating EphA7 to induce appropriate myoblast apoptosis

2019 ◽  
Vol 27 (5) ◽  
pp. 1644-1659 ◽  
Author(s):  
Yaping Nie ◽  
Shufang Cai ◽  
Renqiang Yuan ◽  
Suying Ding ◽  
Xumeng Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Zinc Finger ◽  
Muscle Development ◽  
Zinc Finger Protein ◽  
Critical Role ◽  
Muscle Differentiation ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Finger Protein

Abstract Zinc finger protein 422 (Zfp422) is a widely expressed zinc finger protein that serves as a transcriptional factor to regulate downstream gene expression, but until now, little is known about its roles in myogenesis. We found here that Zfp422 plays a critical role in skeletal muscle development and regeneration. It highly expresses in mouse skeletal muscle during embryonic development. Specific knockout of Zfp422 in skeletal muscle impaired embryonic muscle formation. Satellite cell-specific Zfp422 deletion severely inhibited muscle regeneration. Myoblast differentiation and myotube formation were suppressed in Zfp422-deleted C2C12 cells, isolated primary myoblasts, and satellite cells. Chromatin Immunoprecipitation Sequencing (ChIP-Seq) revealed that Zfp422 regulated ephrin type-A receptor 7 (EphA7) expression by binding an upstream 169-bp DNA sequence, which was proved to be an enhancer of EphA7. Knocking EphA7 down in C2C12 cells or deleting Zfp422 in myoblasts will inhibit cell apoptosis which is required for myoblast differentiation. These results indicate that Zfp422 is essential for skeletal muscle differentiation and fusion, through regulating EphA7 expression to maintain proper apoptosis.

scholarly journals Cadherins Promote Skeletal Muscle Differentiation in Three-dimensional Cultures

1997 ◽  
Vol 138 (6) ◽  
pp. 1323-1331 ◽  
Author(s):  
Ann Redfield ◽  
Marvin T. Nieman ◽  
Karen A. Knudsen
Keyword(s):  
Skeletal Muscle ◽  
Cell Adhesion ◽  
Three Dimensional ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Skeletal Myogenesis ◽  
Bhk Cells ◽  
Vitro Model ◽  
Cell Cell

The cell–cell adhesion molecule N-cadherin, with its associated catenins, is expressed by differentiating skeletal muscle and its precursors. Although N-cadherin's role in later events of skeletal myogenesis such as adhesion during myoblast fusion is well established, less is known about its role in earlier events such as commitment and differentiation. Using an in vitro model system, we have determined that N-cadherin– mediated adhesion enhances skeletal muscle differentiation in three-dimensional cell aggregates. We transfected the cadherin-negative BHK fibroblastlike cell line with N-cadherin. Expression of exogenous N-cadherin upregulated endogenous β-catenin and induced strong cell–cell adhesion. When BHK cells were cultured as three-dimensional aggregates, N-cadherin enhanced withdrawal from the cell cycle and stimulated differentiation into skeletal muscle as measured by increased expression of sarcomeric myosin and the 12/101 antigen. In contrast, N-cadherin did not stimulate differentiation of BHK cells in monolayer cultures. The effect of N-cadherin was not unique since E-cadherin also increased the level of sarcomeric myosin in BHK aggregates. However, a nonfunctional mutant N-cadherin that increased the level of β-catenin failed to promote skeletal muscle differentiation suggesting an adhesion-competent cadherin is required. Our results suggest that cadherin-mediated cell–cell interactions during embryogenesis can dramatically influence skeletal myogenesis.

scholarly journals MicroRNA-24-3p promotes skeletal muscle differentiation and regeneration by regulating HMGA1

2021 ◽  
Author(s):  
Paromita Dey ◽  
Miles A Soyer ◽  
Bijan K Dey
Keyword(s):  
Skeletal Muscle ◽  
Tibialis Anterior Muscle ◽  
High Mobility ◽  
Muscle Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Muscle Stem Cells ◽  
Downstream Target

Abstract Numerous studies have established the critical roles of microRNAs in regulating posttranscriptional gene expression in diverse biological processes. Here, we report on the role and mechanism of miR-24-3p in skeletal muscle differentiation and regeneration. miR-24-3p promotes myoblast differentiation and skeletal muscle regeneration by directly targeting high mobility group AT-hook 1 (HMGA1) and regulating it and its direct downstream target, the inhibitor of differentiation 3 (ID3). miR-24-3p knockdown in neonatal mice increases PAX7-positive proliferating muscle stem cells (MuSCs) by derepressing Hmga1 and Id3 . Similarly, inhibiting miR24-3p in the tibialis anterior muscle prevents Hmga1 and Id3 downregulation and impairs regeneration. These findings provide evidence that the miR-24-3p/HMGA1/ID3 axis is required for MuSC differentiation and regeneration in vivo .

scholarly journals IRE1-XBP1 Pathway of the Unfolded Protein Response Is Required during Early Differentiation of C2C12 Myoblasts

2019 ◽  
Vol 21 (1) ◽  
pp. 182 ◽  
Author(s):  
Yukako Tokutake ◽  
Keita Yamada ◽  
Satoko Hayashi ◽  
Wataru Arai ◽  
Takafumi Watanabe ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Differentiation ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Cyclin Dependent Kinase ◽  
Early Differentiation ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

In skeletal muscle, myoblast differentiation results in the formation of multinucleated myofibers. Although recent studies have shown that unfolded protein responses (UPRs) play an important role in intracellular remodeling and contribute to skeletal muscle differentiation, the involvement of IRE1–XBP1 signaling, a major UPR signaling pathway, remains unclear. This study aimed to investigate the effect of the IRE1–XBP1 pathway on skeletal muscle differentiation. In C2C12 cells, knockdown of IRE1 and XBP1 in cells remarkably suppressed differentiation. In addition, apoptosis and autophagy were dramatically enhanced in the XBP1-knockdown cells, highlighting the participation of IRE1–XBP1 in cell survival maintenance with differentiation stimuli during skeletal muscle differentiation. In myogenic cells, we demonstrated that the expression of CDK5 (cyclin-dependent kinase 5) is regulated by XBP1s, and we propose that XBP1 regulates the expression of MyoD family genes via the induction of CDK5. In conclusion, this study revealed that IRE1–XBP1 signaling plays critical roles in cell viability and the expression of differentiation-related genes in predifferentiated myoblasts and during the early differentiation phase.

scholarly journals Increase in p202 Expression during Skeletal Muscle Differentiation: Inhibition of MyoD Protein Expression and Activity by p202

1998 ◽  
Vol 18 (2) ◽  
pp. 1074-1083 ◽  
Author(s):  
Bansidhar Datta ◽  
Wang Min ◽  
Sandeep Burma ◽  
Peter Lengyel
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Activity ◽  
Muscle Protein ◽  
Specific Binding ◽  
Muscle Differentiation ◽  
Myoblast Differentiation ◽  
Gene Overexpression ◽  
Skeletal Muscle Differentiation ◽  
C2c12 Myoblasts ◽  
Transfected Cells

ABSTRACT p202 is a primarily nuclear, interferon-inducible murine protein that is encoded by the Ifi 202 gene. Overexpression of p202 in transfected cells retards cell proliferation. p202 modulates the pattern of gene expression by inhibiting the activity of various transcription factors including NF-κB, c-Fos, c-Jun, E2F-1, and p53. Here we report that p202 was constitutively expressed in mouse skeletal muscle and that the levels of 202 RNA and p202 greatly increased during the differentiation of cultured C2C12 myoblasts to myotubes. When overexpressed in transfected myoblasts, p202 inhibited the expression of one muscle protein (MyoD) without affecting the expression of a second one (myogenin). Thus, the decrease in the level of MyoD (but not of myogenin) during muscle differentiation may be the consequence of the increase in p202 level. Overexpressed p202 also inhibited the transcriptional activity of both MyoD and myogenin. This inhibition was correlated with an interaction of p202 with both proteins, as well as the inhibition by p202 of the sequence-specific binding of both proteins to DNA. This inhibition of the expression of MyoD and of the transcriptional activity of MyoD and myogenin may account for the inhibition of the induction of myoblast differentiation by premature overexpression of p202.

scholarly journals The histone methyltransferase Set7/9 promotes myoblast differentiation and myofibril assembly

2011 ◽  
Vol 194 (4) ◽  
pp. 551-565 ◽  
Author(s):  
Yazhong Tao ◽  
Ronald L. Neppl ◽  
Zhan-Peng Huang ◽  
Jianfu Chen ◽  
Ru-Hang Tang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Myogenic Differentiation ◽  
Muscle Differentiation ◽  
Histone Methyltransferase ◽  
Contractile Proteins ◽  
Dominant Negative ◽  
Myoblast Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Muscle Gene Expression

The molecular events that modulate chromatin structure during skeletal muscle differentiation are still poorly understood. We report in this paper that expression of the H3-K4 histone methyltransferase Set7 is increased when myoblasts differentiate into myotubes and is required for skeletal muscle development, expression of muscle contractile proteins, and myofibril assembly. Knockdown of Set7 or expression of a dominant-negative Set7 mutant impairs skeletal muscle differentiation, accompanied by a decrease in levels of histone monomethylation (H3-K4me1). Set7 directly interacts with MyoD to enhance expression of muscle differentiation genes. Expression of myocyte enhancer factor 2 and genes encoding contractile proteins is decreased in Set7 knockdown myocytes. Furthermore, we demonstrate that Set7 also activates muscle gene expression by precluding Suv39h1-mediated H3-K9 methylation on the promoters of myogenic differentiation genes. Together, our experiments define a biological function for Set7 in muscle differentiation and provide a molecular mechanism by which Set7 modulates myogenic transcription factors during muscle differentiation.

scholarly journals MicroRNA-24-3p promotes skeletal muscle differentiation and regeneration by regulating high mobility group AT-hook 1

2020 ◽  
Author(s):  
Paromita Dey ◽  
Bijan K. Dey
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
High Mobility ◽  
Muscle Differentiation ◽  
High Mobility Group ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Skeletal Muscle Differentiation

AbstractSkeletal muscle regenerates throughout the lifetime to maintain normal development, growth, and physiological function. Skeletal muscle regeneration occurs in a coordinated fashion and requires strict regulation of myogenic gene expression during the process. Numerous studies have established the critical role of microRNAs in regulating post-transcriptional gene expression in diverse biological processes including differentiation, development, and regeneration. We have revealed in an earlier study that a large number of microRNAs were differentially expressed during myoblast differentiation. Here, we report the role of one such microRNA, the miR-24-3p, in skeletal muscle differentiation and regeneration. miR-24-3p is induced during myoblast differentiation and skeletal muscle regeneration. Exogenous miR-24-3p promotes while inhibition of miR-24-3p represses myoblast differentiation. miR-24-3p promotes myoblast differentiation by directly targeting and regulating the high mobility group AT-hook 1 (HMGA1). Consistent with the finding that HMGA1 is a repressor of myogenic differentiation, the miR-24-3p-resistant form of HMGA1 devoid of 3’untranslated region, inhibits myoblast differentiation. Intramuscular injection of antagomirs specific to miR-24-3p into the tibialis anterior muscle prevents HMGA1 down-regulation and impairs regeneration. These findings provide evidence for the requirement of the miR-24-3p/HMGA1 axis for skeletal muscle differentiation and regeneration.

Die Expression der Aurora Kinase A korreliert mit dem Wnt-Modulator RACGAP1 im Magenkarzinom

2015 ◽  
Vol 53 (08) ◽  
Author(s):  
J Bornschein ◽  
J Nielitz ◽  
I Drozdov ◽  
M Selgrad ◽  
T Wex ◽  
...  
Keyword(s):  
Aurora Kinase ◽  
Aurora Kinase A ◽  
Kinase A
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