Abstract:
:The LIM motif defines a double zinc finger structure found in proteins involved in cell fate determination and growth control. LIM proteins, which include LIM homeo domain, LIM kinase, focal adhesion, and LIM-only proteins, usually contain two or more LIM motifs clustered at their amino- or carboxy-terminal end. At present, the mode of action of the LIM domain is not clear. In this study we have analyzed the binding properties of LIM motifs in the cellular environment. We show that MLP, CRP, and betaCRP define a subclass of LIM-only proteins with unique dual subcellular localization in the nucleus and along actin-based filaments in the cytosol. A double MLP construct that accumulated nearly exclusively along actin filaments promoted myogenic differentiation efficiently, arguing for a functional role of cytoskeleton-associated MLP. Binding of MLP to the actin cytoskeleton is specifically attributable to its second LIM motif. An additional LIM motif potentiates binding. Potentiating LIM motifs can be interchanged, resulting in differential targeting of interacting proteins. To analyze LIM-LIM interactions in situ, this property was exploited to develop a hybrid interaction approach based on the relocalization of LIM-containing constructs to the actin cytoskeleton. These experiments revealed the existence of marked selectivity in the interactions of single LIM motifs, and among LIM domains from different LIM-homeo domain and LIM-only proteins. Furthermore, the analysis suggested that the LIM motif has two interacting interfaces. On the basis of these findings, we propose that LIM motifs function as specific adapter elements to promote the assembly and targeting of multiprotein complexes.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Arber S,Caroni Pdoi
10.1101/gad.10.3.289subject
Has Abstractpub_date
1996-02-01 00:00:00pages
289-300issue
3eissn
0890-9369issn
1549-5477journal_volume
10pub_type
杂志文章abstract::Early endoderm formation in zebrafish requires at least three loci that function downstream of Nodal signaling but upstream of the early endodermal marker sox17: bonnie and clyde (bon), faust (fau), and casanova (cas). cas mutants show the most severe phenotype as they do not form any gut tissue and lack all sox17 exp...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.892301
更新日期:2001-06-15 00:00:00
abstract::Pre-mRNA splicing is essential for generating mature mRNA and is also important for subsequent mRNA export and quality control. The splicing history is imprinted on spliced mRNA through the deposition of a splicing-dependent multiprotein complex, the exon junction complex (EJC), at approximately 20 nucleotides upstrea...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.260403
更新日期:2003-04-15 00:00:00
abstract::Polycomb response elements (PREs) are specific cis-regulatory sequences needed for transcriptional repression of HOX and other target genes by Polycomb group (PcG) proteins. Among the many PcG proteins known in Drosophila, Pho is the only sequence-specific DNA-binding protein. To gain insight into the function of Pho,...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.377406
更新日期:2006-05-01 00:00:00
abstract::The bcl-6 proto-oncogene encodes a POZ/zinc finger transcriptional repressor expressed in germinal center (GC) B and T cells and required for GC formation and antibody affinity maturation. Deregulation of bcl-6 expression by chromosomal rearrangements and point mutations of the bcl-6 promoter region are implicated in ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.13.1953
更新日期:1998-07-01 00:00:00
abstract::Many short-lived mRNAs, including those encoding lymphokines, cytokines, and proto-oncogenes, contain an AU-rich sequence in their 3'-untranslated regions. These AU domains and, more specifically, AUUUA motifs within them, are widely thought to mediate the extreme instability of the corresponding mRNAs. This is most c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.10.1927
更新日期:1992-10-01 00:00:00
abstract::Genomic imprinting is an epigenetic process regulated by germline-derived DNA methylation, causing parental origin-specific monoallelic gene expression. Zinc finger protein 57 (ZFP57) is critical for maintenance of this epigenetic memory during post-fertilization reprogramming, yet incomplete penetrance of ZFP57 mutat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.320069.118
更新日期:2019-01-01 00:00:00
abstract::Nuclear export factor 1 (NXF1) exports mRNA to the cytoplasm after recruitment to mRNA by specific adaptor proteins. How and why cells use numerous different export adaptors is poorly understood. Here we critically evaluate members of the SR protein family (SRSF1-7) for their potential to act as NXF1 adaptors that cou...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.276477.115
更新日期:2016-03-01 00:00:00
abstract::A long-standing model postulates that X-chromosome dosage compensation in Drosophila occurs by twofold up-regulation of the single male X, but previous data cannot exclude an alternative model, in which male autosomes are down-regulated to balance gene expression. To distinguish between the two models, we used RNA int...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1343705
更新日期:2005-10-01 00:00:00
abstract::Alu repetitive sequences are the most abundant short interspersed DNA elements in the human genome. Full-length Alu elements are composed of two tandem sequence monomers, the left and right Alu arms, both derived from the 7SL signal recognition particle RNA. Since Alu elements are common in protein-coding genes, they ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.197467.112
更新日期:2012-09-01 00:00:00
abstract::PIWI clade Argonaute proteins silence transposon expression in animal gonads. Their target specificity is defined by bound ∼23- to 30-nucleotide (nt) PIWI-interacting RNAs (piRNAs) that are processed from single-stranded precursor transcripts via two distinct pathways. Primary piRNAs are defined by the endonuclease Zu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.267252.115
更新日期:2015-08-15 00:00:00
abstract::Multidimensional cancer genome analysis and validation has defined Quaking (QKI), a member of the signal transduction and activation of RNA (STAR) family of RNA-binding proteins, as a novel glioblastoma multiforme (GBM) tumor suppressor. Here, we establish that p53 directly regulates QKI gene expression, and QKI prote...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.189001.112
更新日期:2012-07-01 00:00:00
abstract::Mammalian development requires effective mechanisms to repress genes whose expression would generate inappropriately specified cells. The Polycomb-repressive complex 1 (PRC1) family complexes are central to maintaining this repression. These include a set of canonical PRC1 complexes, each of which contains four core p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.326488.119
更新日期:2019-07-01 00:00:00
abstract::The integration of viral DNA into the host genome is an essential step in the retrovirus life cycle. To understand this process better, we have examined the native state of viral DNA in cells acutely infected by murine leukemia virus (MLV), using both a physical assay for viral DNA and a functional assay for integrati...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.4.469
更新日期:1989-04-01 00:00:00
abstract::Activation of p53-mediated transcription is a critical cellular response to DNA damage. p53 stability and site-specific DNA-binding activity and, therefore, transcriptional activity, are modulated by post-translational modifications including phosphorylation and acetylation. Here we show that p53 is acetylated in vitr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.18.2831
更新日期:1998-09-15 00:00:00
abstract::The Komeda miniature rat Ishikawa (KMI) is a naturally occurring mutant caused by an autosomal recessive mutation mri, which exhibits longitudinal growth retardation. Here we identified the mri mutation as a deletion in the rat gene encoding cGMP-dependent protein kinase type II (cGKII). KMIs showed an expanded growth...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1224204
更新日期:2004-10-01 00:00:00
abstract::DOCK180 is involved in integrin signaling through CrkII-p130(Cas) complexes. We have studied the involvement of DOCK180 in Rac1 signaling cascades. DOCK180 activated JNK in a manner dependent on Rac1, Cdc42Hs, and SEK, and overexpression of DOCK180 increased the amount of GTP-bound Rac1 in 293T cells. Coexpression of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.21.3331
更新日期:1998-11-01 00:00:00
abstract::Estrogen receptor α (ER) is the major driver of ∼75% of breast cancers, and multiple ER targeting drugs are routinely used clinically to treat patients with ER+ breast cancer. However, many patients relapse on these targeted therapies and ultimately develop metastatic and incurable disease, and understanding the mecha...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.316646.118
更新日期:2018-09-01 00:00:00
abstract::DNA methylation is tightly regulated throughout mammalian development, and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested to protect CG dinucleotide (...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.260174.115
更新日期:2015-05-01 00:00:00
abstract::We describe three strains of transgenic mice derived by embryo microinjection of DNA consisting of a long terminal repeat (LTR) of Moloney murine sarcoma virus (Mo-MSV) linked to the murine c-mos coding sequences. Southern analysis of the genomic DNA of these strains suggested that in each case the transgene had integ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.10.1327
更新日期:1987-12-01 00:00:00
abstract::Macrophages play critical roles in events ranging from host defense to obesity and cancer, where they infiltrate affected tissues and orchestrate immune responses in tandem with the remodeling of the extracellular matrix (ECM). Despite the dual roles played by macrophages in inflammation, the functions of macrophage-d...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.178749.111
更新日期:2012-02-15 00:00:00
abstract::Pcf11 is one of numerous proteins involved in pre-mRNA 3'-end processing and transcription termination. Using elongation complexes (ECs) formed from purified yeast RNA polymerase II (Pol II), we show that a 140-amino acid polypeptide from yeast Pcf11 is capable of dismantling the EC in vitro. This action depends on th...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1296305
更新日期:2005-07-01 00:00:00
abstract::We have analyzed pre-mRNA splicing in yeast extracts immunodepleted of the PRP18 protein. We find that while the first step of splicing (cleavage at the 5' splice site, and generation of the exon 1 and lariat intermediates) is unaffected by the absence of PRP18, the second step of splicing (excision of the lariat intr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.2.320
更新日期:1993-02-01 00:00:00
abstract::Neuronal depolarization and CaM kinase IV signaling alter the splicing of multiple exons in transcripts for ion channels, neurotransmitter receptors, and other synaptic proteins. These splicing changes are mediated in part by special CaM kinase-responsive RNA elements, within or adjacent to exons that are repressed in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1837009
更新日期:2009-10-01 00:00:00
abstract::Mediator was resolved from yeast as a multiprotein complex on the basis of its requirement for transcriptional activation in a fully defined system. Three groups of mediator polypeptides could be distinguished: the products of five SRB genes, identified as suppressors of carboxy-terminal domain (CTD)-truncation mutant...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.1.45
更新日期:1998-01-01 00:00:00
abstract::Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.287404
更新日期:2004-06-15 00:00:00
abstract::RNase MRP is a ribonucleoprotein endoribonuclease that has been shown to cleave mitochondrial primer RNA sequences from a variety of sources. Most of the RNase MRP activity is found in the nucleus where it plays a role in the processing of 5.8S rRNA. A temperature-conditional point mutation in the yeast RNA component ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.21.2617
更新日期:1994-11-01 00:00:00
abstract::Nuclear pore complexes (NPCs) emerged as nuclear transport channels in eukaryotic cells ∼1.5 billion years ago. While the primary role of NPCs is to regulate nucleo-cytoplasmic transport, recent research suggests that certain NPC proteins have additionally acquired the role of affecting gene expression at the nuclear ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.280941.116
更新日期:2016-05-15 00:00:00
abstract::Staurosporine, a potent inhibitor of protein kinase C, arrests fission yeast cell elongation specifically at a stage immediately after cell division. We isolated two genes, which, when carried on multicopy plasmids, confer drug resistance in fission yeast. One, spk1+, encodes a protein kinase highly similar (54% ident...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.1.60
更新日期:1991-01-01 00:00:00
abstract::The mitotic kinase Aurora A (Aur-A) is required for formation of a bipolar mitotic spindle and accurate chromosome segregation. In somatic cells, Aur-A protein and kinase activity levels peak during mitosis, and Aur-A is degraded during mitotic exit. Here, we investigated how Aur-A protein and kinase activity levels a...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1007302
更新日期:2002-09-01 00:00:00
abstract::Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ), the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.237628.114
更新日期:2014-05-01 00:00:00