Abstract:
:Numerous studies indirectly implicate Rac GTPases in cancer. To investigate if Rac3 contributes to normal or malignant cell function, we generated rac3 null mutants through gene targeting. These mice were viable, fertile, and lacked an obvious external phenotype. This shows Rac3 function is dispensable for embryonic development. Bcr/Abl is a deregulated tyrosine kinase that causes chronic myelogenous leukemia and Ph-positive acute lymphoblastic leukemia in humans. Vav1, a hematopoiesis-specific exchange factor for Rac, was constitutively tyrosine phosphorylated in primary lymphomas from Bcr/Abl P190 transgenic mice, suggesting inappropriate Rac activation. rac3 is expressed in these malignant hematopoietic cells. Using lysates from BCR/ABL transgenic mice that express or lack rac3, we detected the presence of activated Rac3 but not Rac1 or Rac2 in the malignant precursor B-lineage lymphoblasts. In addition, in female P190 BCR/ABL transgenic mice, lack of rac3 was associated with a longer average survival. These data are the first to directly show a stimulatory role for Rac in leukemia in vivo. Moreover, our data suggest that interference with Rac3 activity, for example, by using geranyl-geranyltransferase inhibitors, may provide a positive clinical benefit for patients with Ph-positive acute lymphoblastic leukemia.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Cho YJ,Zhang B,Kaartinen V,Haataja L,de Curtis I,Groffen J,Heisterkamp Ndoi
10.1128/MCB.25.13.5777-5785.2005subject
Has Abstractpub_date
2005-07-01 00:00:00pages
5777-85issue
13eissn
0270-7306issn
1098-5549pii
25/13/5777journal_volume
25pub_type
杂志文章abstract::The Mauriceville retroplasmid of Neurospora mitochondria encodes a novel reverse transcriptase that initiates cDNA synthesis de novo (i.e., without a primer) at the 3' CCA of the plasmid transcript's 3' tRNA-like structure (H. Wang and A. M. Lambowitz, Cell 75:1071-1081, 1993). Here, we show that the plasmid reverse t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.8.4526
更新日期:1997-08-01 00:00:00
abstract::Previous work showed that tunicamycin suppresses glycosylation of laminin. In the present work, the role of glycosylation in the secretion of laminin and in the disulfide bonding of laminin subunits was studied, using tunicamycin to inhibit glycosylation. Tunicamycin inhibited extensively the secretion of laminin into...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.1.1
更新日期:1984-01-01 00:00:00
abstract::STAT3 is a ubiquitous transcription factor that is indispensable during early embryogenesis. To study the functions of STAT3 postnatally, we generated conditional STAT3-deficient mice. To that end, STAT3(lox/lox) mice were crossed with mice expressing Cre under the control of rat insulin II gene promoter (RIP-Cre mice...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.1.258-269.2004
更新日期:2004-01-01 00:00:00
abstract::The apoptotic process is accompanied by major changes in chromatin structure and gene expression. The apoptotic genetic program is progressively set up with the inhibition of antiapoptotic genes and the activation of proapoptotic ones. Here, we show that the histone deacetylase 3 (HDAC-3), which is a known co-represso...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00869-06
更新日期:2007-01-01 00:00:00
abstract::Lactose or galactose induces the expression of the lactose-galactose regulon in Kluyveromyces lactis. We show here that the regulon is not induced in strains defective in LAC9. We demonstrate that this gene codes for a regulatory protein that acts in a positive manner to induce transcription. The LAC9 gene was isolate...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.3.1111
更新日期:1987-03-01 00:00:00
abstract::Nuclear receptor corepressors (N-CoR) and silencing mediator for retinoid and thyroid receptors (SMRT) have both been implicated in thyroid hormone receptor (TR)-mediated repression. Here we show that endogenous N-CoR, TBL1, and histone deacetylase 3 (HDAC3), but not HDAC1, -2, or -4, are recruited to a stably integra...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.15.5122-5131.2003
更新日期:2003-08-01 00:00:00
abstract::RSC is an essential, multisubunit chromatin remodeling complex. We show here that the Rsc4 subunit of RSC interacted via its C terminus with Rpb5, a conserved subunit shared by all three nuclear RNA polymerases (Pol). Furthermore, the RSC complex coimmunoprecipitated with all three RNA polymerases. Mutations in the C ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00415-06
更新日期:2006-07-01 00:00:00
abstract::Maintaining optimal bone integrity, mass, and strength throughout adult life requires ongoing bone remodeling, which involves coordinated activity between actions of bone-resorbing osteoclasts and bone forming-osteoblasts. Osteoporosis is a disorder of remodeling in which bone resorption outstrips deposition, leading ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06361-11
更新日期:2012-01-01 00:00:00
abstract::While it is well appreciated that receptors for secreted cytokines transmit ligand-induced signals, little is known about additional roles for cytokine receptor components in the control of ligand transport and secretion. Here, we show that interleukin-15 (IL-15) translocation into the endoplasmic reticulum occurs ind...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02178-07
更新日期:2008-08-01 00:00:00
abstract::To investigate in vivo roles of a murine hypothalamic homeobox gene, Bsx, we generated and analyzed two mutant alleles, Bsx(DeltaHD) and Bsx(lacZ). Bsx(DeltaHD) lacks the homeodomain, and Bsx(lacZ) is an insertion of a lacZ reporter gene. Bsx-lacZ expression was detected in the hypothalamus and pineal gland and reiter...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00215-07
更新日期:2007-07-01 00:00:00
abstract::Temperature-sensitive mutants of TFIIB that are defective for essential interactions were isolated. One mutation (G204D) results in disruption of a protein-protein contact between TFIIB and TATA binding protein (TBP), while the other (K272I) disrupts an interaction between TFIIB and DNA. The TBP gene was mutagenized, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.24.8735-8743.2002
更新日期:2002-12-01 00:00:00
abstract::In eukaryotes, crossovers in mitotic cells can have deleterious consequences and therefore must be suppressed. Mutations in BLM give rise to Bloom syndrome, a disease that is characterized by an elevated rate of crossovers and increased cancer susceptibility. However, simple eukaryotes such as Saccharomyces cerevisiae...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.9.3431-3442.2005
更新日期:2005-05-01 00:00:00
abstract::The positively acting regulatory gene amdR of Aspergillus nidulans coordinately regulates the expression of five structural genes involved in the catabolism of certain amides (amdS), omega amino acids (gatA and gabA), and lactams (lamA and lamB) in the presence of omega amino acid inducers. Analysis of the amdR gene s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.6.3194
更新日期:1990-06-01 00:00:00
abstract::The micronemal protein 2 (MIC2) of Toxoplasma gondii shares sequence and structural similarities with a series of adhesive molecules of different apicomplexan parasites. These molecules accumulate, through a yet unknown mechanism, in secretory vesicles (micronemes), which together with tubular and membrane structures ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.19.7332-7341.2000
更新日期:2000-10-01 00:00:00
abstract::In Saccharomyces cerevisiae, a phosphorelay signal transduction pathway composed of Sln1p, Ypd1p, and Ssk1p, which are homologous to bacterial two-component signal transducers, is involved in the osmosensing mechanism. In response to high osmolarity, the phosphorelay system is inactivated and Ssk1p remains unphosphory...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.18.6662-6671.2003
更新日期:2003-09-01 00:00:00
abstract::Ischemia in the heart deprives cardiomyocytes of oxygen, triggering cell death (myocardial infarction). Ischemia and its cell culture model, hypoxia, elicit a stress response program that contributes to cardiomyocyte death; however, the molecular components required to promote this process remain nebulous. Gene 33 is ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02387-05
更新日期:2006-07-01 00:00:00
abstract::To interrogate endogenous p21(WAF1/CIP1) (p21) promoter activity under basal conditions and in response to various forms of stress, knock-in imaging reporter mice in which expression of firefly luciferase (FLuc) was placed under the control of the endogenous p21 promoter within the Cdkn1a gene locus were generated. Bi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.05243-11
更新日期:2011-09-01 00:00:00
abstract::Much of the regulatory diversity in eukaryotic transcription is provided by coregulators, which are recruited by DNA-binding factors to propagate signaling to basal machinery or chromatin. p160 family members, including the glucocorticoid receptor (GR)-interacting protein 1 (GRIP1), function as coactivators for GR, a ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06473-11
更新日期:2012-02-01 00:00:00
abstract::The tumor suppressor p21 acts as a cell cycle inhibitor and has also been shown to regulate gene expression by functioning as a transcription corepressor. Here, we identified p21-regulated microRNAs (miRNAs) by sequencing small RNAs from isogenic p21(+/+) and p21(-/-) cells. Three abundant miRNA clusters, miR-200b-200...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01043-13
更新日期:2014-02-01 00:00:00
abstract::Sequence data are presented for the Saccharomyces cerevisiae TAP1 gene and for a mutant allele, tap1-1, that activates transcription of the promoter-defective yeast SUP4 tRNA(Tyr) allele SUP4A53T61. The degree of in vivo activation of this allele by tap1-1 is strongly affected by the nature of the flanking DNA sequenc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.6.3434
更新日期:1993-06-01 00:00:00
abstract::Runx1/AML1 is a transcription factor implicated in tissue stem cell regulation and belongs to the small Runx family of cancer genes. In the hair follicle (HF), Runx1 epithelial deletion in morphogenesis impairs normal adult hair homeostasis (cycle) and blocks adult hair follicle stem cells (HFSCs) in quiescence. Here,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01308-09
更新日期:2010-05-01 00:00:00
abstract::The extracellular matrix (ECM) promotes tissue morphogenesis, cell migration, and the differentiation of a variety of cell types. However, the mechanisms by which ECM causes differentiated gene expression have been unknown. In this report, we show that culturing the hepatocyte-derived cell line H2.35 on an ECM gel cha...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.9.4405
更新日期:1991-09-01 00:00:00
abstract::The chaperone-related AAA ATPase Cdc48 (p97/VCP in higher eukaryotes) segregates ubiquitylated proteins for subsequent degradation by the 26S proteasome or for nonproteolytic fates. The specific outcome of Cdc48 activity is controlled by the evolutionary conserved cofactors Ufd2 and Ufd3, which antagonistically regula...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00962-10
更新日期:2011-04-01 00:00:00
abstract::We have initiated a study of the promoter region of the alkaline extracellular protease gene (XPR2) from Yarrowia lipolytica to identify upstream sequences possibly involved in carbon, nitrogen, and peptone control of XPR2 expression. Deletion analysis showed that the TATA box and two major upstream activation sequenc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.1.327
更新日期:1994-01-01 00:00:00
abstract::The recombinant shuttle vector pSV2gpt was introduced into V79 Chinese hamster cells, and stable transformants expressing the Escherichia coli gpt gene were selected. Two transformants carrying tandem duplications of the plasmid at a single site were identified and fused to simian COS-1 cells. Plasmid DNA recovered fr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.11.2266
更新日期:1984-11-01 00:00:00
abstract::The large T antigen of simian virus 40 (SV40) is a multifunctional protein that is essential in both the virus lytic cycle and the oncogenic transformation of cells by SV40. To investigate the role of the numerous biochemical and physiological activities of T antigen in the lytic and transformation processes, we have ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.6.1125
更新日期:1984-06-01 00:00:00
abstract::Fragments of 5'-flanking and noncoding exon I sequences of the human gastrin gene were analyzed in transient expression assays after transfection of a variety of cell lines with the pSVCAT vector system. In the presence of the simian virus 40 (SV40) enhancer, the gastrin gene fragment from nucleotides -250 to +57, rel...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.12.4329
更新日期:1987-12-01 00:00:00
abstract::The relationship between chromatin remodeling and histone acetylation at the yeast CUP1 gene was addressed. CUP1 encodes a metallothionein required for cell growth at high copper concentrations. Induction of CUP1 with copper resulted in targeted acetylation of both H3 and H4 at the CUP1 promoter. Nucleosomes containin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.18.6406-6416.2002
更新日期:2002-09-01 00:00:00
abstract::We delimited sequences necessary for in vivo expression of the Drosophila melanogaster dopa decarboxylase gene Ddc. The expression of in vitro-altered genes was assayed following germ line integration via P-element vectors. Sequences between -209 and -24 were necessary for normally regulated expression, although genes...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.12.4548
更新日期:1986-12-01 00:00:00
abstract::Densely methylated DNA sequence islands, designated DMIs, have been observed in two Chinese hamster cell chromosomal replication origins by using a PCR-based chemical method of detection. One of the origins, oriS14, is located within or adjacent to the coding sequence for ribosomal protein S14 on chromosome 2q, and th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.9.5636
更新日期:1994-09-01 00:00:00