Identification of a novel vimentin promoter and mRNA isoform

Zhou, Zhangle; Kahns, Søren; Nielsen, Anders Lade

doi:10.1007/s11033-009-9751-8

Cited by 15 publications

(12 citation statements)

References 36 publications

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“…A clear difference in the HP1α gene H3‐K36 trimethylation level was observed between MDA‐MB‐231 and MCF‐7 cells with more H3‐K36 trimethylation present in MCF‐7 cells. The H3‐K36 trimethylation profiles are in accordance with observations of other genes showing correspondence between mRNA levels and the H3‐K36 trimethylation profile [35]. ChIP analysis showed that RNA pol‐II was present throughout the HP1α gene to lesser extend in MDA‐MB‐231 cells compared with MCF‐7 cells.…”

Section: Discussionsupporting

confidence: 85%

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Analysis of HP1α regulation in human breast cancer cells

Thomsen

Christensen

Rosborg

et al. 2011

Molecular Carcinogenesis

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The three mammalian HP1 proteins, HP1α/CBX5, HP1β/CBX1, and HPγ/CBX3, are involved in chromatin packing and gene regulation. The HP1α protein is down-regulated in invasive compared to non-invasive breast cancer cells and HP1α is a suppressor of cell migration and invasion. In this report, we examined the background for HP1α protein down-regulation in invasive breast cancer cells. We identified a strict correlation between HP1α down-regulation at the protein level and the mRNA level. The HP1α mRNA down-regulation in invasive cancer cells was not caused by mRNA destabilization. Chromatin immunoprecipitation analysis of the HP1α gene showed a decrease in the histone mark for transcriptional activity H3-K36 tri-methylation and RNA polymerase II in invasive breast cancer cells which correlated with a decreased abundance of basal transcription factors at the HP1α promoter. E2F transcription factors regulate HP1α transcription and we identified that E2F5 depletion increased HP1α expression in invasive breast cancer cells. Finally, we have characterized two HP1α mRNA isoforms and both HP1α mRNA isoforms were down-regulated to a similar extend at the transcriptional level in invasive breast cancer cells. Collectively the presented results show that HP1α down-regulation in invasive breast cancer cells is primary a transcriptional effect and demonstrates a novel set of mechanisms involved in HP1α transcriptional regulation. The finding that HP1α is down-regulated primarily at the transcriptional level provides a new insight for the further elucidation of the detailed molecular mechanisms causing the HP1α down-regulation in invasive breast cancer cells.

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Section: Discussionsupporting

confidence: 85%

“…ChIP analyses were done essential as previously described [35]. In summary, ChIP was performed with 10 mL cultures fixed with 1% formaldehyde for 10 min followed by addition of glycine to 0.25 mM final concentration.…”

Section: Methodsmentioning

confidence: 99%

Analysis of HP1α regulation in human breast cancer cells

Thomsen

Christensen

Rosborg

et al. 2011

Molecular Carcinogenesis

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“…4C). Of those, 24 were identified as isoforms of the protein vimentin (VIM), previously described as being expressed as different isoforms due to alternative splicing [25] or different phosphorylation states of the protein [26]. The majority of the VIM isoforms (n = 19) show a lower content in P7 compared to P3 (Table 1, Fig.…”

Section: Resultsmentioning

confidence: 99%

Human Mesenchymal Stem Cell Expression Program upon Extended Ex-Vivo Cultivation, as Revealed by 2-DE-Based Quantitative Proteomics

et al. 2012

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Human mesenchymal stem cells (MSC) have been on the focus of intense clinical-oriented research due to their multilineage differentiation potential and immunomodulatory properties. However, to reach the clinically meaningful cell numbers for cellular therapy and tissue engineering applications, MSC ex-vivo expansion is mandatory but sequential cell passaging results in loss of proliferative, clonogenic and differentiation potential. To get clues into the molecular mechanisms underlying cellular senescence resulting from extended ex-vivo cultivation of bone marrow (BM) MSC, we explored a two-dimensional gel electrophoresis (2-DE) based quantitative proteomics to compare the expression programs of Passage 3 cells (P3), commonly used in clinical studies with expanded MSC, and Passage 7 (P7) cells, which already demonstrated significant signs of culture-induced senescence. Proteins of the functional categories “Structural components and cellular cytoskeleton” and “Folding and stress response proteins” are less abundant in P7 cells, compared to P3, while proteins involved in “Energy metabolism”, “Cell cycle regulation and aging” and “Apoptosis” are more abundant. The large number of multiple size and charge isoforms with an altered content that were identified in this study in P7 versus P3, namely the cytoskeleton components β-actin (7 forms) and vimentin (24 forms), also emphasizes the importance of post-transcriptional modification upon long-term cultivation. The differential protein expression registered suggests that cellular senescence occurring during ex-vivo expansion of BM MSC is associated with the impairment of cytoskeleton remodeling and/or organization and the repair of damaged proteins resulting from cell exposure to culture stress. The genome-wide expression approach used in this study has proven useful for getting mechanistic insights into the observed decrease on the proliferative and clonogenic potential of P7 versus P3 cells and paves the way to set up a proteome profiling strategy for quality control to assure safe and clinically effective expanded MSC.

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“…Keratin, vimentin, desmin, lamin, peripherin and GFAP are all alternatively spliced (Landon et al, 1989;Langbein et al, 2010;Lin and Worman, 1993;Park et al, 2000;Zhou et al, 2010). There are multiple splice variants of GFAP, including , , , ,  and  (Blechingberg et al, 2007; Condorelli et al, 1999; Feinstein et al, 1992;Nielsen et al, 2002;Zelenika et al, 1995) among others.…”

Section: Regulation Of If Interactions and Assembly By Alternative Spmentioning

confidence: 99%

Insights into intermediate filament regulation from development to ageing

Hyder

Isoniemi

Torvaldson

et al. 2011

Journal of Cell Science

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SummaryIntermediate filament (IF) proteins comprise a large family with more than 70 members. Initially, IFs were assumed to provide only structural reinforcement for the cell. However, IFs are now known to be dynamic structures that are involved in a wide range of cellular processes during all stages of life, from development to ageing, and during homeostasis and stress. This Commentary discusses some lesser-known functional and regulatory aspects of IFs. We specifically address the emerging roles of nestin in myogenesis and cancer cell migration, and examine exciting evidence on the regulation of nestin and lamin A by the notch signalling pathway, which could have repercussions for our understanding of the roles of IF proteins in development and ageing. In addition, we discuss the modulation of the post-translational modifications of neuronally expressed IFs and their protein-protein interactions, as well as IF glycosylation, which not only has a role in stress and ageing, but might also regulate IFs during development. Although many of these recent findings are still preliminary, they nevertheless open new doors to explore the functionality of the IF family of proteins. Journal of Cell ScienceCdk5 is associated with nestin in myoblasts, neuronal precursor cells (Sahlgren et al., 2003) and human podocytes (Bertelli et al., 2007). Cdk5 phosphorylates nestin, and this phosphorylation regulates the organization of nestin filaments (Box 2) during myogenic differentiation (Sahlgren et al., 2003). Interestingly, the interaction between nestin and Cdk5 is not limited to a typical kinase-substrate relationship. In neuronal precursor cells, nestin forms a scaffold for Cdk5 and the Cdk5 activator p35, thereby sequestering them to the cytoplasm, which consequently inhibits the proapoptotic function of Cdk5 during oxidative stress (Sahlgren et al., 2006). In turn, it has recently been demonstrated that Cdk5 is targeted by protein kinase C- (PKC) during myogenesis (de Thonel et al., 2010). PKC is essential for proper myoblast differentiation. It targets Cdk5 by phosphorylating p35 at a site that triggers the activation of calpains, which then cleave p35 into p25. The cleavage of p35 into p25 creates a more stable protein fragment, and this fragment is capable of sustained Cdk5 activation, consequently promoting nestin reorganization (Fig. 1,. An earlier study, in cultured neurons, demonstrated that Cdk5 is also able to regulate p35 by phosphorylation, thereby protecting it from calpain-mediated cleavage (Kamei et al., 2007). Furthermore, a recent study has shown that nestin has the capacity to modulate Cdk5-mediated differentiation and terminal organization of muscle cells (Pallari et al., 2011) (Fig. 1, left-hand side). Taken together, these results suggest that a balance between Cdk5 and PKC is important for proper myogenic differentiation, as they show that disturbance of the PKC-Cdk5-nestin signalling pathway leads to nestin reorganization and impedes myoblast differentiation, implying that nestin also plays a k...

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Identification of a novel vimentin promoter and mRNA isoform

Cited by 15 publications

References 36 publications

Analysis of HP1α regulation in human breast cancer cells

Analysis of HP1α regulation in human breast cancer cells

Human Mesenchymal Stem Cell Expression Program upon Extended Ex-Vivo Cultivation, as Revealed by 2-DE-Based Quantitative Proteomics

Insights into intermediate filament regulation from development to ageing

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