Abstract:
:Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a member of the nuclear receptor superfamily of transcription factors. In most cases the PR is induced by estrogen, implying that many of the in vivo effects attributed to progesterone could also be the result of concomitantly administered estrogen. Therefore, to clearly define those physiological events that are specifically attributable to progesterone in vivo, we have generated a mouse model carrying a null mutation of the PR gene using embryonic stem cell/gene targeting techniques. Male and female embryos homozygous for the PR mutation developed normally to adulthood. However, the adult female PR mutant displayed significant defects in all reproductive tissues. These included an inability to ovulate, uterine hyperplasia and inflammation, severely limited mammary gland development, and an inability to exhibit sexual behavior. Collectively, these results provide direct support for progesterone's role as a pleiotropic coordinator of diverse reproductive events that together ensure species survival.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Lydon JP,DeMayo FJ,Funk CR,Mani SK,Hughes AR,Montgomery CA Jr,Shyamala G,Conneely OM,O'Malley BWdoi
10.1101/gad.9.18.2266subject
Has Abstractpub_date
1995-09-15 00:00:00pages
2266-78issue
18eissn
0890-9369issn
1549-5477journal_volume
9pub_type
杂志文章abstract::The agouti gene regulates the differential production of eumelanin (black or brown) and phaeomelanin (yellow) pigment granules by melanocytes in the hair follicles of mice. The original nonagouti (a) allele, which confers a predominantly black coat color, has been shown to revert to two other more dominant agouti alle...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.4.481
更新日期:1994-02-15 00:00:00
abstract::Post-translational modifications of histones are significant regulators of replication, transcription, and DNA repair. Particularly, newly synthesized histone H4 in H3/H4 heterodimers becomes acetylated on N-terminal lysine residues prior to its incorporation into chromatin. Previous studies have established that the ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.240531.114
更新日期:2014-06-01 00:00:00
abstract::Cell cycle progression is dependent on two major waves of gene expression. Early cell cycle gene expression occurs during G1/S to generate factors required for DNA replication, while late cell cycle gene expression begins during G2 to prepare for mitosis. Here we demonstrate that the MuvB complex-comprised of LIN9, LI...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.181933.111
更新日期:2012-03-01 00:00:00
abstract::AAUAAA is the most highly conserved motif in eukaryotic mRNA polyadenylation sites and, in mammals, is specifically recognized by the multisubunit CPSF (cleavage and polyadenylation specificity factor) complex. Despite its critical functions in mRNA 3' end formation, the molecular basis for CPSF-AAUAAA interaction rem...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.250993.114
更新日期:2014-11-01 00:00:00
abstract::Chromosomal translocations are a hallmark of hematopoietic malignancies. The initial molecular events or pathways that lead to translocations in hematopoietic cells are largely unknown, particularly in the stem cell-enriched population postulated to be the initial target for these events. We used in vitro differentiat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1522807
更新日期:2007-05-01 00:00:00
abstract::Disruption of the balanced modulation of reversible tyrosine phosphorylation has been implicated in the etiology of various human cancers, including breast cancer. Protein Tyrosine Phosphatase N23 (PTPN23) resides in chromosomal region 3p21.3, which is hemizygously or homozygously lost in some breast cancer patients. ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.304261.117
更新日期:2017-10-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDA) develops predominantly through pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) precursor lesions. Pancreatic acinar cells are reprogrammed to a "ductal-like" state during PanIN-PDA formation. Here, we demonstrate a parallel mechanis...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.256628.114
更新日期:2015-03-15 00:00:00
abstract::The mouse Nedd5 gene encodes a 41.5-kD GTPase similar to the Saccharomyces and Drosophila septins essential for cytokinesis. Nedd5 accumulates near the contractile ring from anaphase through telophase, and finally condenses into the midbody. Microinjection of anti-Nedd5 antibody interferes with cytokinesis, giving ris...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.12.1535
更新日期:1997-06-15 00:00:00
abstract::In yeast, galactose triggers a rapid GAL4-dependent induction of galactose/melibiose regulon (GAL/MEL) gene transcription, and glucose represses this activation. We discovered that alterations in the physical state of the GAL4 protein correlate with activation and repression of the GAL/MEL genes. Using Western immunob...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.8.1157
更新日期:1989-08-01 00:00:00
abstract::In murine plasmacytoma and human Burkitt's lymphoma cells, one allele of c-myc is translocated into one of the immunoglobulin loci, resulting in a characteristic pattern of deregulated c-myc transcription. Translocation events between c-myc and the IgH locus segregate c-myc and the IgH intron enhancer to different rec...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.18.2212
更新日期:1994-09-15 00:00:00
abstract::The retinoblastoma tumor suppressor (pRb) protein associates with chromatin and regulates gene expression. Numerous studies have identified Rb-dependent RNA signatures, but the proteomic effects of Rb loss are largely unexplored. We acutely ablated Rb in adult mice and conducted a quantitative analysis of RNA and prot...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.264127.115
更新日期:2015-09-01 00:00:00
abstract::The C-terminal domain of the Escherichia coli RNA polymerase (RNAP) alpha subunit (alphaCTD) stimulates transcription initiation by interacting with upstream (UP) element DNA and a variety of transcription activators. Here we identify specific substitutions in region 4.2 of sigma 70 (sigma(70)) and in alphaCTD that de...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1079403
更新日期:2003-05-15 00:00:00
abstract::We have developed a simple, effective genetic screen for mutant alleles of eukaryotic DNA topoisomerase I that manifest severely depressed or complete loss of enzymatic function. The screen is based on the extreme toxicity of vaccinia topoisomerase expression in the Escherichia coli lysogen strain BL21(DE3) and is not...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.4.515
更新日期:1990-04-01 00:00:00
abstract::We have developed a new technique, called 'toeprinting,' which has allowed a study of the tRNA-binding properties of Escherichia coli translation initiation complexes. In response to natural mRNAs, the initiator tRNA and a variety of elongator tRNAs bind to the same tRNA-binding site on the 30S ribosomal subunit as lo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.12a.1899
更新日期:1989-12-01 00:00:00
abstract::Human TFIIA activity is composed of three subunits (alpha, beta, gamma). Here we report the isolation of a human cDNA clone encoding the gamma-subunit and the reconstitution of TFIIA activity from recombinant polypeptides (holo-TFIIA). Protein-protein interaction analysis established that the beta and gamma subunits o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.19.2336
更新日期:1994-10-01 00:00:00
abstract::Telomerase is a ribonucleoprotein enzyme that adds telomeric repeats to chromosomes, maintaining telomere length and stabilizing chromosome ends. In vitro, telomerase from the ciliate Tetrahymena elongates single-stranded, guanosine-rich DNA primers by adding repeats of the Tetrahymena telomeric sequence, dT2G4. We ha...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.7b.1364
更新日期:1993-07-01 00:00:00
abstract::Cellular morphology is an essential determinant of cellular function in all kingdoms of life, yet little is known about how cell shape is controlled. Here we describe a molecular program that controls the early morphology of neurons through a metazoan-specific zinc finger protein, Unkempt. Depletion of Unkempt in mous...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.258483.115
更新日期:2015-03-01 00:00:00
abstract::DBP (albumin D-site-binding protein), HLF (hepatic leukemia factor), and TEF (thyrotroph embryonic factor) are the three members of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family. All three of these transcriptional regulatory proteins accumulate with robust circadian...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.301404
更新日期:2004-06-15 00:00:00
abstract::Pax6 is a key transcription factor in eye development, particularly in lens development, but its molecular action has not been clarified. We demonstrate that Pax6 initiates lens development by forming a molecular complex with SOX2 on the lens-specific enhancer elements, e.g., the delta-crystallin minimal enhancer DC5....
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.887101
更新日期:2001-05-15 00:00:00
abstract::The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs). Seven genes (smg-1-7, for suppressor with morphological effect on genitalia) that are essential for NMD were originally identified in the nematode Caenorhabditis elegans, and orthologs of these gene...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.417707
更新日期:2007-05-01 00:00:00
abstract::The transformer-2 (tra-2) gene of Drosophila melanogaster plays essential roles in both sexual differentiation in the female soma and spermatogenesis in the male germ line. In the female soma, tra-2 is known to act with other genes in the sex determination regulatory cascade to control the sex-specific alternative spl...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.5.789
更新日期:1990-05-01 00:00:00
abstract::Ste5, the prototypic mitogen-activated protein kinase (MAPK) scaffold protein, associates with plasma membrane-tethered Gbetagamma freed upon pheromone receptor occupancy, thereby initiating downstream signaling. We demonstrate that this interaction and membrane binding of an N-terminal amphipathic alpha-helix (PM mot...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1413706
更新日期:2006-07-15 00:00:00
abstract::Endospores of Bacillus subtilis are encased in a two-layer protein shell known as the coat, which consists of a lammellar-like inner layer and an electron-dense outer layer. We report the cloning of the structural gene (designated cotE) for an alkali-soluble coat protein of 24 kD and show that the cotE gene product is...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.8.1047
更新日期:1988-08-01 00:00:00
abstract::Somitogenesis involves the segmentation of the paraxial mesoderm into units along the anteroposterior axis. Here we show a role for Eph and ephrin signaling in the patterning of presomitic mesoderm and formation of the somites. Ephrin-A-L1 and ephrin-B2 are expressed in an iterative manner in the developing somites an...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.19.3096
更新日期:1998-10-01 00:00:00
abstract::Mismatch repair (MMR) has important roles in meiotic and mitotic recombination, DNA damage signaling, and various aspects of DNA metabolism including class-switch recombination, somatic hypermutation, and triplet-repeat expansion. Defects in MMR are responsible for human cancers characterized by microsatellite instabi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.430107
更新日期:2007-09-01 00:00:00
abstract::The female mammary gland is a very dynamic organ that undergoes continuous tissue remodeling during adulthood. Although it is well established that the number of menstrual cycles and pregnancy (in this case transiently) increase the risk of breast cancer, the reasons are unclear. Growing clinical and experimental evid...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.292318.116
更新日期:2017-03-15 00:00:00
abstract::Structural cell-surface and extracellular-matrix proteins modulate intercellular signaling events during development, but how this is achieved remains largely unknown. Here we identify a novel family of Drosophila proteins, Nasrat and Polehole, that coat the oocyte surface and play two roles: They mediate assembly of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.223902
更新日期:2002-04-15 00:00:00
abstract::Glucocorticoid (GC) receptor (GR) has been shown recently to bind a subset of mRNAs and elicit rapid mRNA degradation. However, the molecular details of GR-mediated mRNA decay (GMD) remain unclear. Here, we demonstrate that GMD triggers rapid degradation of target mRNAs in a translation-independent and exon junction c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.286484.116
更新日期:2016-09-15 00:00:00
abstract::Treatment with retinoic acid (RA) is known to produce complex teratogenic effects in vertebrates, and its presence in the developing embryo as an endogenous substance has led to the suggestion that RA might be a natural morphogenetic agent. Although our understanding of the molecular mechanism of RA action has improve...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.8.1333
更新日期:1991-08-01 00:00:00
abstract::In petunia flowers, the loci an1, an2, and an11 control the pigmentation of the flower by stimulating the transcription of anthocyanin biosynthetic genes. The an1 and an2 locus were recently cloned and encode a basic helix-loop-helix (bHLH) and MYB-domain transcriptional activator, respectively. Here, we report the is...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.11.1422
更新日期:1997-06-01 00:00:00