scholarly journals The nuclear activity of the actin‐binding Moesin protein is necessary for gene expression in Drosophila

FEBS Journal ◽  
2021 ◽  
Author(s):  
Csaba Bajusz ◽  
Ildikó Kristó ◽  
Csilla Abonyi ◽  
Tomáš Venit ◽  
Viktor Vedelek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Actin Binding ◽  
Nuclear Activity

scholarly journals Cytoskeletal proteins in the cell nucleus: a special nuclear actin perspective

2019 ◽  
Vol 30 (15) ◽  
pp. 1781-1785 ◽  
Author(s):  
Piergiorgio Percipalle ◽  
Maria Vartiainen
Keyword(s):  
Gene Expression ◽  
Cell Nucleus ◽  
Cell Biology ◽  
Genome Stability ◽  
Actin Polymerization ◽  
Nuclear Architecture ◽  
Nuclear Lamina ◽  
Cytoskeletal Proteins ◽  
Actin Binding ◽  
Special Focus

The emerging role of cytoskeletal proteins in the cell nucleus has become a new frontier in cell biology. Actin and actin-binding proteins regulate chromatin and gene expression, but importantly they are beginning to be essential players in genome organization. These actin-based functions contribute to genome stability and integrity while affecting DNA replication and global transcription patterns. This is likely to occur through interactions of actin with nuclear components including nuclear lamina and subnuclear organelles. An exciting future challenge is to understand how these actin-based genome-wide mechanisms may regulate development and differentiation by interfering with the mechanical properties of the cell nucleus and how regulated actin polymerization plays a role in maintaining nuclear architecture. With a special focus on actin, here we summarize how cytoskeletal proteins operate in the nucleus and how they may be important to consolidate nuclear architecture for sustained gene expression or silencing.

Functional analysis of MKL1/2, actin-binding coactivators for SRF, in neuronal morphology and gene expression

2007 ◽  
Vol 58 ◽  
pp. S142
Author(s):  
Naoki Nishijima ◽  
Mitsuru Ishikawa ◽  
Hiroyuki Tsutsumishita ◽  
Jun Shiota ◽  
Masaaki Tsuda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Functional Analysis ◽  
Neuronal Morphology ◽  
Actin Binding

scholarly journals Nuclear-capture of endosomes drives depletion of nuclear G-actin to promote SRF/MRTF gene expression and cancer cell invasiveness

2020 ◽  
Author(s):  
Sergi Marco ◽  
Matthew Neilson ◽  
Madeleine Moore ◽  
Arantxa Pérez-García ◽  
Holly Hall ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Import ◽  
Tyrosine Kinases ◽  
Target Genes ◽  
Serum Response Factor ◽  
Actin Binding ◽  
Cell Scattering ◽  
Nuclear Localisation Sequence ◽  
Related Transcription Factor ◽  
Cell Invasiveness

Abstract Signals are relayed from receptor tyrosine kinases (RTKs) at the cell surface to effector systems in the cytoplasm and nucleus, and coordination of this process is important for the execution of migratory phenotypes, such as cell scattering and invasion. The endosomal system influences how RTK signalling is coded, but the ways in which it transmits these signals to the nucleus to influence gene expression are not yet clear. Here we show that an RTK, cMET promotes Rab17-dependent endocytosis of EphA2, another RTK, followed by centripetal transport of EphA2-positive endosomes. EphA2 then mediates physical capture of endosomes on the outer surface of the nucleus; a process involving interaction between the nuclear import machinery and a nuclear localisation sequence in EphA2’s cytodomain. Nuclear capture of EphA2 promotes RhoG-dependent phosphorylation of the actin-binding protein, cofilin to oppose nuclear import of G-actin. The resulting depletion of nuclear G-actin drives transcription of Myocardin-related transcription factor (MRTF)/serum-response factor (SRF)-target genes to implement cell scattering and the invasive behaviour of cancer cells.

Use of tumor gene expression signatures and drug-induced changes to discriminate early response in human breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2524-2524
Author(s):  
S. Lee ◽  
M. Watson ◽  
X. Xu ◽  
C. I. Wong ◽  
P. Iau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Calcium Binding ◽  
Early Response ◽  
Actin Binding ◽  
Expression Ratio ◽  
Pre Treatment ◽  
Tumor Gene Expression ◽  
Tumor Gene

2524 Background: To elucidate the genomics of tumor responses to different classes of chemotherapy, we analyzed breast cancer gene expression before and after in vivo treatment with adriamycin or docetaxel. Methods: Tumor biopsies were obtained before and 3 weeks after one chemotherapy cycle and tumor RNA amplified and hybridized on the Affymetrix HG-U133+2 array containing 33,000 genes. Results: Pre- and post-treatment tumors from 46 chemonaive patients with unresectable breast cancers were studied, of which 24 and 22 respectively received adriamycin and docetaxel in the first cycle, and 14 in each group had early response sensitive tumors (=25% shrinkage after 1 cycle). Comparison of our baseline gene signatures with drug-specific panels generated in vitro (Nevins, Nat Med 2006,12:1294) revealed 12 and 2 common genes (p<0.05) that predicted for adriamycin and docetaxel response respectively, with the 12 common adriamycin-response gene panel correctly predicting response in 76% of patients. Analysis of the relative change in tumor gene expression (ratio of post- and pre-treatment differential values to pre-treatment values) in our dataset revealed adriamycin to up- or down- regulate 209 transcripts (p<0.005) including genes that encode for nuclear protein, cell cycle regulation, aminopeptidases, and Ankyrin repeats, while docetaxel up- or down-regulated 469 transcripts (p<0.005) including genes that encode for extracellular matrix, transmembrane signaling, endocytosis, EGF-like calcium binding, tubulin and actin binding functions. Adriamycin and docetaxel concordantly up- or down-regulated 269 transcripts (p<0.01) that may be common response markers, including genes involved in cell cycle proliferation, mitosis, DNA damage, and carboxypeptidase activities. Adriamycin and docetaxel differentially induced 92 transcripts (p<0.01) that distinguished between the two drugs with 96% accuracy. 27 adriamycin- and 100 docetaxel-induced transcripts (p<0.005) predicted response to each drug with >90% accuracy. Conclusions: Drug-specific genomic changes can predict clinical response, and may yield insights to targets to overcome drug resistance. No significant financial relationships to disclose.

Gata-Independent Regulation of Red Cell Specific Gene Expression.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1736-1736
Author(s):  
Jenna L. Galloway ◽  
Rebecca A. Wingert ◽  
Christine Thisse ◽  
Bernard Thisse ◽  
Leonard I. Zon
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Regulation Of Gene Expression ◽  
Actin Binding ◽  
Specific Gene ◽  
Cellular Functions ◽  
Novel Genes ◽  
Independent Manner ◽  
Repeat Protein ◽  
Gata Factors

Abstract During vertebrate embryonic hematopoiesis, the first blood cells can be identified by expression of the transcription factor genes scl and GATA2, followed by expression of GATA1, a gene required for the erythroid lineage. A high-throughput in situ hybridization screen in zebrafish analyzed the expression pattern of 3700 clones from a hematopoietic cDNA library and discovered 24 genes with expression in the blood. Examination of gene expression in Biklf, GATA1, GATA2, and GATA1/GATA2-deficient animals revealed that most blood genes are dependent upon GATA factors for expression rather than the Krüppel-like transcription factor Biklf. Three novel genes, expressed specifically in erythroid precursors, did not require GATA factors for their expression, demonstrating that some blood genes are regulated in a GATA-independent manner. These three genes were kelch-repeat protein (kelch repeats have been implicated in diverse cellular functions from actin binding to sequestering transcriptions factors), kiaa0650, which contains an SMC-hinge domain, and testhymin, which has no known structural motifs. By using combinations of antisense morpholinos to the known hematopoietic genes biklf , GATA1, GATA2, and scl, we were able to examine the regulation of these novel genes in double and triple knock-down embryos. While expression of kelch-repeat protein was lost in the absence of GATA1 and Biklf, expression of testhymin and kiaa0650 was maintained in GATA1/GATA2/Biklf-deficient embryos, suggesting that these similarly expressed genes are differentially regulated. As with GATA1, kiaa0650 and kelch-repeat protein required Scl for their expression in the early hematopoietic mesoderm while testhymin did not. Furthermore, loss of Scl and GATA2 did not completely ablate testhymin expression, suggesting that this gene is induced by factors upstream or parallel to Scl and GATA2. Taken together, our zebrafish studies establish a regulation of gene expression by a developmental hierarchy of specific transcription factors that act in combination during blood cell maturation.

New Insights into Deregulated Gene Expression Pathways in MLL- and AF10-Rearranged T-Lineage Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2906-2906
Author(s):  
Huining Kang ◽  
Nitesh Sharma ◽  
Christian K Nickl ◽  
Scott Ness ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Signaling Pathways ◽  
Rna Binding ◽  
Lymphoblastic Leukemia ◽  
Differentially Expressed ◽  
Actin Binding ◽  
Molecular Features ◽  
Laboratory Services ◽  
Therapeutic Decisions

Abstract For children, adolescents and young adults with T-lineage acute lymphoblastic leukemia, event free survival (EFS) following relapse is <10%. We recently showed that MLL-AF6, del3'MLL and other re-arrangements of the mixed lineage leukemia (MLL-R; KMT2A) molecular repertoire are associated with induction failure (IF) and an inferior EFS (Matlawska-Wasowska et al., Leukemia, 2016). However, we found that AF10 (MLLT10) gene structural alterations (AF10-R) did not confer a worse prognosis. While deregulation of HOXA9/10 is a hallmark of all MLL-R and AF10 lesions, its over-expression does not predict outcome or guide therapeutic decisions. Because there are currently no molecular features that inform treatment strategies in T-ALL, we hypothesized that supervised profiling of well-characterized cases might identify biologically relevant genes and signaling pathways for targeted T-ALL therapy. Using Affymetrix U133 Plus 2.0 microarray we performed a retrospective study of 100 T-ALL patients enrolled onto COG ALL0434. We performed a 3-way analysis of MLL-R Cases (n = 12), AF10-R Cases (n = 9), and Other T-ALL Cases (n = 79), and identified 330 probe sets that could discriminate between these groups. For the MLL-R Cases and AF10-R Cases, 258 and 40 probe sets, respectively, were uniquely different compared to Other T-ALL Cases. Within the MLL-R Cases group, the most deregulated genes included HOXA genes, MYO6, which encodesATP-dependent motor protein, SKAP2, a substrate of Src family kinases, transcriptional/translational regulators RUNX2, TCF4, SMAD1, CPEB2 (> 3-fold, P < 0.05) and interestingly WHAMMP2/WHAMMP3, and GOLGA8I pseudogenes (> 3-fold, P < 0.05). For the AF10-R cases, we found that MEIS1, HOXA3, 5, 7, 9/10, SPAG6, BMI1, and COMMD3 expression were deregulated, similar to the findings of others. We next identified genes that could discriminate between MLL-R and AF10-R cases. Among the most overexpressed genes, we identified MYO6, RUNX2, CPEB2, ZNF827 and TCF4 (> 3-fold, FDR < 0.05) indicating that MLL-R encompass a specific biological subset, which collectively drive a unique oncogenic transcriptional program. The most downregulated gene in both MLL- and AF10-R cases was QKI, which encodes RNA-binding protein involved in alternative splicing (> 3-fold, P < 0.05). Since MLL-AF6 confers an inferior outcome, we sought to determine which genes discriminate between MLL-AF6 (n = 5) and MLL-ENL (n = 5). Among the 26 discriminatory probes sets, we found two, MLLT4 and uncharacterized RP11-38P22 that were over-expressed and 24 were underexpressed, including SMAD1, CHI3L2, MYOM2 between AF6 and ENL, respectively (> 10 fold change, FDR < 0.05). As an extension of the study we performed Gene Set Enrichment Analyses to assess functional networks. Genes that were differentially expressed in MLL-R cases were enriched in regulators of secretion and endocytosis (NES = 1.84, FDR = 0.06), actin binding and cytoskeleton function (NES = 1.7, FDR ≤ 0.25), embryonic development (NES = 1.98, FDR ≤ 0.25), and genes upregulated by hedgehog signaling pathways (NES = 1.73, FDR ≤ 0.25). Genes that were differentially expressed in AF10-R include those that activate cytokine production (NES = 1.90, FDR ≤ 0.25). Taken together, these pathways are commonly targeted by inhibitors of kinase signaling pathways and the proteosome. In summary, we have identified an extended repertoire of aberrant gene expression in MLL-R and AF10-R T-ALL. Our findings provide a mechanistic basis for additional pre-clinical testing of in classes of therapeutic agents that may hold promise for high-risk T-ALL. Disclosures Wood: Juno: Other: Laboratory Services Agreement; Seattle Genetics: Honoraria, Other: Laboratory Services Agreement; Amgen: Honoraria, Other: Laboratory Services Agreement; Pfizer: Honoraria, Other: Laboratory Services Agreement. Asselin:Sigma Tau Pharamceuticals: Consultancy; Jazz Pharmaceuticals: Consultancy, Speakers Bureau. Loh:Abbvie: Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees.

The Drosophila forked protein induces the formation of actin fiber bundles in vertebrate cells

1999 ◽  
Vol 112 (13) ◽  
pp. 2203-2211 ◽  
Author(s):  
S. Grieshaber ◽  
N.S. Petersen
Keyword(s):  
Gene Expression ◽  
Developmental Biology ◽  
Proximal Tubule ◽  
Actin Polymerization ◽  
Actin Binding ◽  
Fiber Bundles ◽  
Actin Bundle ◽  
Actin Binding Protein ◽  
Kidney Proximal Tubule ◽  
Actin Fiber

The forked protein is an actin binding protein involved in the formation of large actin fiber bundles in developing Drosophila bristles. These are the largest example of a type of actin bundle characterized by parallel, hexagonally packed actin fibers, also found in intestinal microvilli, kidney proximal tubule microvilli, and stereocilia in the ear. Understanding how these structures are constructed and how that construction is regulated is an important question in cell and developmental biology. Because the timing of forked gene expression coincides with the formation of the actin fiber bundles, and since the forked protein is localized at the site of initiation of these bundles before they form, it has been proposed that the forked protein is an initiator of actin bundle formation. In this paper we show that the forked protein can induce the formation of bundles and increase actin polymerization in vertebrate cells. We use this system to identify regions of the forked protein which are essential for bundle formation and actin co-localization.

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