The cytoskeletal protein Zyxin interacts with the zinc-finger transcription factor Zic1 and plays the role of a scaffold for Gli1 and Zic1 interactions during early development of Xenopus laevis

Martynova, Natalia Y.; Parshina, Elena A.; Ermolina, L. V.; Zaraisky, Andrey G.

doi:10.1016/j.bbrc.2018.08.164

Cited by 9 publications

(8 citation statements)

References 22 publications

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“…As zyxin does not have a canonical nuclear localization signal (NLS), shuttling between focal adhesions and the nucleus should be mediated by unconventional mechanisms or through association with NLS containing proteins 12 . Although the role of zyxin in the nucleus is still unclear, evidences obtained from other members of the zyxin family migrating to the nucleus support the idea that these proteins interact with transcription factors or the basal transcription machinery to regulate gene expression 12 – 14 . Studies performed with cells susceptible to high stretch showed translocation of zyxin to the nucleus upon cell stretching, where it influenced the expression of more than 400 genes mostly related with inhibition of apoptosis and proliferation, reinforcement of ECM interactions and proinflammatory response 15 , 16 .…”

Section: Introductionmentioning

confidence: 97%

Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival

2020

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Proteases modulate critical processes in cutaneous tissue repair to orchestrate inflammation, cell proliferation and tissue remodeling. However, the functional consequences and implications in healing impairments of most cleavage events are not understood. Using iTRAQ-based Terminal Amine Isotopic Labeling of Substrates (TAILS) we had characterized proteolytic signatures in a porcine wound healing model and identified two neoN termini derived from proteolytic cleavage of the focal adhesion protein and mechanotransducer zyxin. Here, we assign these proteolytic events to the activity of either caspase-1 or serine protease HtrA1 and analyze the biological relevance of the resultant zyxin truncations. By cellular expression of full-length and truncated zyxin proteins, we demonstrate nuclear translocation of a C-terminal zyxin fragment that could also be generated in vitro by HtrA1 cleavage and provide evidence for its anti-apoptotic activities, potentially by regulating the expression of modulators of cell proliferation, protein synthesis and genome stability. Targeted degradomics correlated endogenous generation of the same zyxin fragment with increased cell density in human primary dermal fibroblasts. Hence, this newly identified HtrA1-zyxin protease signaling axis might present a novel mechanism to transiently enhance cell survival in environments of increased cell density like in wound granulation tissue.

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Section: Introductionmentioning

confidence: 97%

Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival

2020

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“…Therefore, there is lack of other evidence in human cancers that identifies the role of CLIPs in JAK-STAT signaling. Similarly, one study reported that the cytoskeletal protein Zyxin is involved in fine tuning the neural plate patterning in Xenopus laevis embryos by modulating the activity of an effector of Hh signaling, the transcription factor glioma-associated oncogene 1 (GLI1) (Martynova et al, 2018). Hh signaling, which results in activation of GLI transcription factors and correlates with worse outcomes of breast cancer, is activated in human mammary stem cells (Bhateja et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

CLIP4 Shows Putative Tumor Suppressor Characteristics in Breast Cancer: An Integrated Analysis

Fan

Wang

et al. 2021

Front. Mol. Biosci.

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Background: CAP-Gly domain containing linker protein family member 4 (CLIP4) plays an important role in cancers. However, its expression, prognostic value, and biological effect in breast cancer remain unclear.Methods: Data on patients diagnosed with breast cancer were retrieved from the TCGA-BRCA and other public omics databases. The expression profile of CLIP4 was analyzed using Oncomine, bc-GenExMiner, and TCGA. The prognostic value of CLIP4 was determined by Kaplan-Meier Plotter and Human Protein Atlas. Identification of genes co-expressed with CLIP4 and potential mechanism analyses were performed using UALCAN, STRING, Metascape, and GSEA. The epigenetic characteristics of CLIP4 were determined by DiseaseMeth and MEXPRESS.Results: CLIP4 was downregulated and its expression was negatively correlated with estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor type 2 (HER2) status, Nottingham prognostic index (NPI), and Scarff-Bloom-Richardson (SBR) grade in breast cancer, whereas it was positively linked to basal-like and triple negative breast cancer status. Ectopic expression of CLIP4 was related with poor prognosis. In the analysis of genes co-expressed with CLIP4, GSEA showed that the Hedgehog (Hh), JAK-STAT, ERBB, Wnt signaling pathway, cell adhesion molecules, and pathways in cancer were dissimilarly enriched in the CLIP4 expression high phenotype. Analysis of the genetics and epigenetics of CLIP4 indicated that its expression was negatively correlated with DNA methylation.Conclusion: Methylated CLIP4 may be a novel prognostic and therapeutic biomarker for breast cancer.

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“…Taking this experience into account in subsequent next work ( Martynova et al, 2018 ), we developed and used the presented protocol and showed that Zyxin can stabilize the complex formed by Zic1 with Gli1. The formation of this Zic1-carrying complex leads to the nuclear accumulation of Gli1 and Zyxin; however, an excess of Zyxin leads to the retention of Gli1 in the cytoplasm.…”

Section: Expected Outcomesmentioning

confidence: 94%

Protocol for separation of the nuclear and the cytoplasmic fractions of Xenopus laevis embryonic cells for studying protein shuttling

2021

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Summary This protocol for the separation of nuclear and cytoplasmic fractions of cells of Xenopus laevis embryos was developed to study changes in the intracellular localization of the Zyxin and Ybx1 proteins, which are capable of changing localization in response to certain stimuli. Western blot analysis allows the quantification of changes in the distribution of these proteins between the cytoplasm and nucleus, whereas the posttranslational modifications specific to each compartment can be identified by changes in electrophoretic mobility. For complete details on the use and execution of this protocol, please refer to Parshina et al. (2020) .

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The cytoskeletal protein Zyxin interacts with the zinc-finger transcription factor Zic1 and plays the role of a scaffold for Gli1 and Zic1 interactions during early development of Xenopus laevis

Cited by 9 publications

References 22 publications

Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival

Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival

CLIP4 Shows Putative Tumor Suppressor Characteristics in Breast Cancer: An Integrated Analysis

Protocol for separation of the nuclear and the cytoplasmic fractions of Xenopus laevis embryonic cells for studying protein shuttling

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