Protein Tyrosine Phosphatase-Like A Regulates Myoblast Proliferation and Differentiation through MyoG and the Cell Cycling Signaling Pathway

Lin, Xi; Yang, Xiangsheng; Li, Qi; Ma, Yanlin; Cui, Shuang; He, Dacheng; Lin, Xia; Schwartz, Robert J.; Chang, Jiang

doi:10.1128/mcb.05484-11

Cited by 27 publications

(30 citation statements)

References 68 publications

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“…Transcripts were quantified by qPCR analysis (StepOnePlus; Life Technologies) using the SYBR Green method with a MasterMix buffer system containing Taq polymerase, as described previously (20). Total RNA was prepared by TRIzol extraction.…”

Section: Methodsmentioning

confidence: 99%

Genetic deletion of Rnd3 results in aqueductal stenosis leading to hydrocephalus through up-regulation of Notch signaling

Lin

Liu

Yang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Rho family guanosine triphosphatase (GTPase) 3 (Rnd3), a member of the small Rho GTPase family, is involved in the regulation of cell actin cytoskeleton dynamics, cell migration, and proliferation through the Rho kinase-dependent signaling pathway. We report a role of Rnd3 in the pathogenesis of hydrocephalus disorder. Mice with Rnd3 genetic deletion developed severe obstructive hydrocephalus with enlargement of the lateral and third ventricles, but not of the fourth ventricles. The cerebral aqueducts in Rnd3-null mice were partially or completely blocked by the overgrowth of ependymal epithelia. We examined the molecular mechanism contributing to this Rnd3-deficiency–mediated hydrocephalus and found that Rnd3 is a regulator of Notch signaling. Rnd3 deficiency, through either gene deletion or siRNA knockdown, resulted in a decrease in Notch intracellular domain (NICD) protein degradation. However, there was no correlated change in mRNA change, which in turn led to an increase in NICD protein levels. Immunoprecipitation analysis demonstrated that Rnd3 and NICD physically interacted, and that down-regulation of Rnd3 attenuated NICD protein ubiquitination. This eventually enhanced Notch signaling activity and promoted aberrant growth of aqueduct ependymal cells, resulting in aqueduct stenosis and the development of congenital hydrocephalus. Inhibition of Notch activity rescued the hydrocephalus disorder in the mutant animals.

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Section: Methodsmentioning

confidence: 99%

Genetic deletion of Rnd3 results in aqueductal stenosis leading to hydrocephalus through up-regulation of Notch signaling

Lin

Liu

Yang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Repressed MYOG expression is responsible for impaired myoblast differentiation (34). The repressed levels of MYOD1 and MYOG imply that the myogenesis process, including differentiation, fusion and growth, was impaired in the concomitant strabismus patients.…”

Section: Discussionmentioning

confidence: 99%

Abnormal expression of seven myogenesis-related genes in extraocular muscles of patients with concomitant strabismus

Zhu

Deng

Long

et al. 2012

Molecular Medicine Reports

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Abstract. Hyperplasia or hypoplasia of muscles gradually leads to strabismus. Myogenesis-related genes are involved in extraocular muscle development, including myogenic differentiation 1 (MYOD1), myogenin (MYOG), retinoblastoma 1 (RB1), cyclin-dependent kinase inhibitor 1A (P21), cyclin-dependent kinase inhibitor 1C (P57), insulin-like growth factor 1 (IGF1) and muscle creatine kinase (MCK). This study evaluated the expression of the above seven myogenesis-related genes by realtime quantitative RT-PCR in 18 resected extrocular muscles of patients with concomitant strabismus and 12 normal control muscle samples from one presumably healthy male 6 h after sudden mortality. We found that although there was a great divergence among the expression levels of 6 myogenesis-related regulatory factors, the relative expression patterns were similar in all the normal muscles, including the synergistic, antagonistic and yoke muscles. However, their expression levels in the 18 diseased extraocular muscles were abnormal; the expression levels of all the genes, with the exception of P57, were reduced in most of the diseased muscle tissues. These results imply that the abnormal expression of these myogenesis-related genes may contribute to concomitant strabismus.

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“…At least 1 × 10 6 synchronized C2C12 cells grown in GM were prepared for the cell cycle analyses as described previously [35] by FACS. Briefly, cells were fixed in 70% ethanol for 30 min at 4 °C and washed in PBS.…”

Section: Methodsmentioning

confidence: 99%

Histone methyltransferase Setd2 is critical for the proliferation and differentiation of myoblasts

Yi¹,

Tao²,

Lin³

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Skeletal muscle cell proliferation and differentiation are tightly regulated. Epigenetic regulation is a major component of the regulatory mechanism governing these processes. Histone modification is part of the epigenetic code used for transcriptional regulation of chromatin through the establishment of an active or repressive state for genes involved in myogenesis in a temporal manner. Here, we uncovered the function of SET domain containing 2 (Setd2), an essential histone 3 lysine 36 trimethyltransferase, in regulating the proliferation and differentiation of myoblasts. Setd2 was silenced in the skeletal muscle myoblast cell line, C2C12, using the CRISPR/CAS9 system. The mutant cells exhibited defect in myotube formation. The myotube formation marker, myosin heavy chain (MHC), was downregulated earlier in Setd2 silenced cells compared to wild-type myoblasts during differentiation. The deficiency in Setd2 also resulted in repression of Myogenin (MyoG) expression, a key myogenic regulator during differentiation. In addition to the myoblast differentiation defect, decreased proliferation rate with significantly reduced levels of histone 3 phosphorylation, indicative of cell proliferation defect, were observed in the Setd2 silenced cells; suggesting an impaired proliferation phenotype. Furthermore, compromised G1/S- and G2/M-phase transition and decreased expression levels of major regulators of cell cycle G1/S checkpoints, cyclin D1, CDK4, CDK6, and cyclin E2 were detected in Setd2 silenced cells. Consistent with the cell cycle arrested phenotype, cyclin-dependent kinase inhibitor p21 was upregulated in Setd2 silenced cells. Together, this study demonstrates an essential role of Setd2 in myoblast proliferation and differentiation, and uncovers Setd2-mediated molecular mechanism through regulating MyoG and p21.

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Protein Tyrosine Phosphatase-Like A Regulates Myoblast Proliferation and Differentiation through MyoG and the Cell Cycling Signaling Pathway

Cited by 27 publications

References 68 publications

Genetic deletion of Rnd3 results in aqueductal stenosis leading to hydrocephalus through up-regulation of Notch signaling

Genetic deletion of Rnd3 results in aqueductal stenosis leading to hydrocephalus through up-regulation of Notch signaling

Abnormal expression of seven myogenesis-related genes in extraocular muscles of patients with concomitant strabismus

Histone methyltransferase Setd2 is critical for the proliferation and differentiation of myoblasts

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