Transgelin: An actin-binding protein and tumour suppressor

Assinder, Stephen J.; Stanton, Jo‐Ann L.; Prasad, Priya D.

doi:10.1016/j.biocel.2008.02.011

Cited by 219 publications

(227 citation statements)

References 25 publications

Supporting

Mentioning

216

Contrasting

Unclassified

Order By: Relevance

“…Given the importance of actin cytoskeleton on cell migration and tumorigenesis, understanding proteins involved in the binding and regulation of actin organization should provide potential tumor markers and targets for treatment regimens. TAGLN, also named the smooth muscle protein 22-a (SM22-a), is an actin stress fiber-associated protein (Assinder et al, 2009). It is frequently downregulated in breast, colon (Shields et al, 2002;Wulfkuhle et al, 2002) and prostate cancers (Yang et al, 2007), where a tumor suppressor function has been proposed.…”

Section: Discussionmentioning

confidence: 99%

“…However, serine residues phosphorylation on TAGLN greatly weakens this actin-binding ability (Assinder et al, 2009). We carried out immunoprecipitation analysis to confirm if TAGLN2 serine phosphorylation has an effect on its actin-binding capability in HCC.…”

Section: Tagln2 and Actin Phosphorylationsmentioning

confidence: 97%

“…Studies on TAGLN have shown that it is an actin fiber-binding protein (Assinder et al, 2009). However, serine residues phosphorylation on TAGLN greatly weakens this actin-binding ability (Assinder et al, 2009).…”

Section: Tagln2 and Actin Phosphorylationsmentioning

confidence: 99%

See 2 more Smart Citations

A novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motility

et al. 2011

View full text Add to dashboard Cite

The PFTK1 gene encodes a cdc2-related serine/threonine protein kinase that has been shown to confer cell migratory properties in hepatocellular carcinoma (HCC). However, the prognostic value and biological mechanism by which PFTK1 promotes HCC motility remain largely unknown. Here, we showed from tissue microarray that common upregulations of PFTK1 in primary HCC tumors (n ¼ 133/180) correlated significantly with early age onset (p40 years), advance tumor grading and presence of microvascular invasion (Pp0.05). To understand downstream phosphorylated substrate(s) of PFTK1, phospho-proteins in PFTK1 expressing and knockdown Hep3B cells were profiled by two-dimensional-polyacrylamide gel electrophoresis mass spectrometric analysis. Protein identification of differential spots revealed b-actin (ACTB) and transgelin2 (TAGLN2) as the two most profound phosphorylated changes affected by PFTK1. We verified the presence of TAGLN2 serine phosphorylation and ACTB tyrosine phosphorylation. Moreover, reduced TAGLN2 and ACTB phosphorylations in PFTK1-suppressed Hep3B corresponded to distinct actin depolymerizations and marked inhibition on cell invasion and motility. Given that TAGLN2 is a tumor suppressor whose function has been ascribed in cancer metastasis, we examined if TAGLN2 is an intermediate substrate in the biological path of PFTK1. We showed in PFTK1-suppressed cells that knockdown of TAGLN2 over-rode the inhibitory effect on cell invasion and motility, and a recovery on actin polymerization was evident. Interestingly, we also found that unphosphorylated TAGLN2 in PFTK1-suppressed cells elicited strong actin-binding ability, a mechanism that possibly halts the actin cytoskeleton dynamics. Site-directed mutagenesis of TAGLN2 suggested that PFTK1 regulates the actinbinding affinity of TAGLN2 through the S83 and S163 residues, which if mutated can significantly affect HCC cell motility. Taken together, our data propose a novel, oncogene-tumor suppressor interplay, where oncogenic PFTK1 confers HCC cell motility through inactivating the actin-binding motile suppressing function of TAGLN2 via phosphorylation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Tagln2 and Actin Phosphorylationsmentioning

confidence: 97%

See 1 more Smart Citation

A novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motility

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Transgelin, an actin-binding protein, has been recognized as a tumour suppressor [38] that specifically inhibits ARA54-enhanced AR transactivation with less severe side effects than those caused by systemic suppression of the AR signalling pathway, especially in many important organs. Transgelin has the advantage of specifically targeting the interaction between ARA54 and AR.…”

Section: Transgelin Upregulated Bax Expression Downregulated Bcl-2 Ementioning

confidence: 99%

Transgelin induces apoptosis of human prostate LNCaP cells through its interaction with p53

Zhang¹,

Yang²,

Zheng³

et al. 2010

Asian J Androl

View full text Add to dashboard Cite

The androgen receptor (AR) and its coregulators have important roles in the carcinogenesis of prostate cancer. p53 is an important tumour suppressor gene, and the absence of a fundamental p53 response may predispose to cancer. Transgelin, known as an ARA54-associated AR inhibitor, can suppress AR function in LNCaP cells. In addition to these effects, we aimed to elucidate the proapoptotic effects of the protein on LNCaP and its underlying mechanisms, especially the interaction between transgelin and p53. Cell counting, flow cytometric analysis and terminal deoxynucleotidyl transferase-dUTP nick-end labelling assays were applied to measure the proapoptotic effect of transgelin. Using western blotting of p53 and double immunofluorescence staining of p53 with transgelin, we show that transfection of transgelin results in increasing cytoplasmic translocation of p53 and upregulation of p53 expression. We also found an interaction between transgelin and p53 in vivo by mammalian two-hybrid and coimmunoprecipitation assays. The activation of the mitochondria-associated apoptosis pathway was observed in LNCaP cells after transfection with transgelin. These results are indicative of p53-mediated mitochondria-associated apoptotic effects of transgelin on LNCaP cells in addition to its known suppressive effects on the AR pathway.

show abstract

“…6,7 A novel marker, transgelin, a 22 kDa actin-binding protein of the calponin family, also correlates with smooth muscle differentiation. 10 The promoter of the gene is the target of the transcriptional activator serum response factor of which myocardin acts as a cofactor. 11 In an unpublished study, Aurias et al (Institut Curie, France), isolated target genes of myocardin through gene expression profiling using sarcoma cell lines and found that transgelin was one of the most represented in leiomyosarcomatous differentiation.…”

mentioning

confidence: 99%

Transgelin is a novel marker of smooth muscle differentiation that improves diagnostic accuracy of leiomyosarcomas: a comparative immunohistochemical reappraisal of myogenic markers in 900 soft tissue tumors

et al. 2013

View full text Add to dashboard Cite

Transgelin: An actin-binding protein and tumour suppressor

Cited by 219 publications

References 25 publications

A novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motility

A novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motility

Transgelin induces apoptosis of human prostate LNCaP cells through its interaction with p53

Transgelin is a novel marker of smooth muscle differentiation that improves diagnostic accuracy of leiomyosarcomas: a comparative immunohistochemical reappraisal of myogenic markers in 900 soft tissue tumors

Contact Info

Product

Resources

About