Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Testis brain RNA-binding protein (TB-RBP) suppresses translation in vitro and attaches mRNAs to microtubules by binding to conserved elements in the 3' untranslated regions (UTRs) of specific testis and brain mRNAs. Purification of TB-RBP from testicular and brain cytoplasmic extracts has revealed that mouse TB-RBP is 99% identical to the human protein translin, a recombination "hot spot" binding protein associated with chromosomal translocations. Using a cDNA encoding TB-RBP, the gene copy number and the developmental expression of TB-RBP have been analyzed by Southern blotting, Northern blotting, and in situ hybridization. In the mouse, TB-RBP is encoded by a single copy gene. In mouse testes, three TB-RBP mRNAs of about 1.2, 1.7, and 3.0 kb are developmentally regulated with high levels of expression in meiotic and postmeiotic germ cells. A fourth TB-RBP transcript of about 3.2 kb is seen in the brain. In situ hybridization confirms high levels of testicular TB-RBP mRNAs in meiotic and postmeiotic cells, with the highest levels of TB-RBP mRNAs in pachytene spermatocytes and round spermatids of the mouse and in round spermatids of the rat. RNase H digestion assays reveal that the three TB-RBP mRNAs of mouse testes result from processing differences in their 3' untranslated regions. These data demonstrate that multiple TB-RBP mRNAs are primarily expressed in meiotic and postmeiotic germ cells in the mammalian testis, and although the specific RNA-binding ability of TB-RBP appears limited to brain and testis, TB-RBP mRNAs are widely expressed.
Mol Reprod Dev 1998 Mar
PMID:The RNA- and DNA-binding protein TB-RBP is spatially and developmentally regulated during spermatogenesis. 949 73

We have previously demonstrated that the basal transcription of rat inhibin alpha-subunit gene in a mouse testicular Leydig tumor cell line, MA-10, depends upon a 67-bp DNA fragment at the position of -163 to -97. Within this promoter region two GATA motifs were observed. In this study, we investigated the possible role of GATA-binding proteins in the regulation of inhibin alpha-subunit gene transcription in testicular cells. Northern blot and RT-PCR analyses showed that mRNAs encoding GATA-binding proteins, GATA-1 and GATA-4, were detected in mouse and rat testis and in MA-10 and rat Sertoli cells. Testis-specific GATA-1 mRNA, which is transcribed from a promoter 8 kb upstream to the erythroid exon I of mouse GATA-1 gene, was also identified in MA-10 cells. Mutations of GATA sequences in alpha-subunit promoter markedly decreased the transcriptional activity of alpha-subunit gene when measured by their ability of transient expression of a bacterial reporter gene, chloramphenicol acetyltransferase (CAT), in MA-10 cells. Cotransfection of alphaCAT chimeric construct with cDNA expression plasmid coding for mouse GATA-1 or GATA-4 protein revealed that GATA-1 but not GATA-4 can transactivate alpha-subunit promoter in a dose-dependent manner. The transactivation by GATA-1 was inhibited if GATA sequences in alpha-subunit promoter were mutated. Furthermore, electrophoretic mobility shift assay demonstrated that GATA-binding proteins present in nuclear extracts of MA-10 cells and rat testis interacted with the GATA motifs in alpha-subunit promoter, and the GATA-1 in these nuclear extracts formed a supershifted immunocomplex with antibody raised against mouse GATA-1 protein. We therefore concluded that the basal transcription of inhibin alpha-subunit gene in testicular MA-10 cells is up-regulated by testicular GATA-1 but not GATA-4 through its interaction with the GATA motifs in alpha-subunit promoter. In summary, we have provided the first evidence of the functional role of a GATA-binding protein in the regulation of testicular gene expression.
Mol Endocrinol 1998 Mar
PMID:Testicular GATA-1 factor up-regulates the promoter activity of rat inhibin alpha-subunit gene in MA-10 Leydig tumor cells. 951 55

The dihydropyrimidinase-related protein (DRP) family, originally identified in humans by their homology to dihydropyrimidinase, contains at least four members. Genes of this family, and their counterparts in other mammals and chickens, are expressed mainly in fetal and neonatal brain, suggesting that the encoded proteins have a physiological role in the development of the central nervous system. In addition, the DRP-3 gene is expressed in testis as a shorter mRNA than the brain form. As a first step in understanding the extra-neuronal function of DRP-3, the structure and expression of testis DRP-3 were examined. Testis DRP-3 cDNA showed the same sequence as brain DRP-3 cDNA, except for the 5'-terminal end, which encodes a 5'-untranslated region and the 11 N-terminal amino acid residues, indicating that the two forms of DRP-3 mRNA were transcribed from a single copy gene. Northern blotting analysis detected DRP-3 mRNA in 30-, 40- and 70-day-old, but not in 10- and 20-day-old testes. In situ hybridization analysis indicated that the expression of DRP-3 in testis is restricted to post-meiotic round spermatids. This is the first report of the expression of DRP genes in extra-neuronal cells.
Mol Reprod Dev 1998 Sep
PMID:Post-meiotic expression of the mouse dihydropyrimidinase-related protein 3 (DRP-3) gene during spermiogenesis. 971 24

The single copy mouse Testis Brain RNA-Binding Protein (TB-RBP) gene encodes three mRNAs of 3.0, 1.7, and 1.0 kb which only differ in their 3' UTRs. The 1 kb TB-RBP mRNA predominates in testis, while somatic cells preferentially express the 3.0 kb TB-RBP mRNA. Here we show that the 1 kb mRNA is translated several-fold more efficiently than the 3 kb TB-RBP in rabbit reticulocyte lysates and cells with elevated levels of the 1 kB TB-RBP mRNA express high levels of TB-RBP. To determine if the cleavage stimulatory factor CstF 64 can modulate the alternative splicing of the TB-RBP pre-mRNA and therefore TB-RBP expression, CstF 64 levels and binding to alternative polyadenylation sites were examined. CstF 64 is abundant in the testis and preferentially binds to a distal site in the TB-RBP pre-mRNA that produces the 3 kb TB-RBP. Moreover, upregulation or overexpression of CstF 64 increases the poly(A) site selection for the 1 kb TB-RBP mRNA. We propose that the level of the polyadenylation factor CstF 64 modulates the level of TB-RBP synthesis in male germ cells by an alternative processing of the TB-RBP pre-mRNA.
Mol Reprod Dev 2001 Apr
PMID:Elevated levels of the polyadenylation factor CstF 64 enhance formation of the 1kB Testis brain RNA-binding protein (TB-RBP) mRNA in male germ cells. 1124 84

The gene CREM plays key physiological and developmental roles within the hypothalamic--pituitary--gonadal axis. We have previously shown that CREM is highly expressed in male postmeiotic cells. Spermiogenesis is a complex process by which postmeiotic male germ cells differentiate into mature spermatozoa. CREM regulates the expression of a number of post-meiotic genes involved in the process of spermiogenesis. Using homologous recombination we have generated CREM-mutant mice that display a complete block at the first step of spermiogenesis. The molecular mechanism by which CREM elicits its regulatory function involves ACT (Activator of CREM in Testis), a testis-specific coactivator constituted by a repeat of four and half LIM domains. ACT is coordinately expressed with CREM, associates with it and confers a powerful transcriptional activation function. It is able to bypass the classical requirement of CREM phosphorylation and recruiting of CBP.
Mol Cell Endocrinol 2001 Jun 20
PMID:Transcriptional cascades during spermatogenesis: pivotal role of CREM and ACT. 1142 Jan 26

FSH has been shown to elicit in vitro changes in the Sertoli cell cytoskeleton through involving proteases, and cytochalasin-D mimics FSH. Testis extracts were screened (RT-PCR) for various metalloproteinases (MMPs), 20-day-old rat Sertoli cells were purified, cultured and treated with FSH, cytochalasin D and TNFalpha (to antagonize FSH action). Cell shape (phase-contrast microscopy) and levels for MMP-2 (gelatin zymography) and its inhibitor TIMP-2 (Northern and Western blot) were monitored. TNFalpha-treated cells spread readily and grew larger than FSH-treated cells. Cytochalasin-D mimicked FSH, and MMP-2 production and TIMP-2 gene expression were augmented. Interestingly, TNFalpha reversed FSH- and cytochalasin D-induced effects both on cell shape and on MMP-2 and TIMP-2. These effects occurred during the first 48 h of culture, when Sertoli cells migrated from the freshly dispersed aggregates, but not once cells were organized in monolayers. MMP-2 and TIMP-2 are likely involved in the FSH-induced changes in Sertoli cells.
Mol Cell Endocrinol 2002 Mar 28
PMID:Evidence that MMP-2 and TIMP-2 are at play in the FSH-induced changes in Sertoli cells. 1203 62

FSH mediates its testicular actions via a specific Sertoli cell G protein-coupled receptor. We created a novel transgenic model to investigate a mutant human FSH receptor (FSHR(+)) containing a single amino acid substitution (Asp567Gly) equivalent to activating mutations in related glycoprotein hormone receptors. To examine the ligand-independent gonadal actions of FSHR(+), the rat androgen-binding protein gene promoter was used to direct FSHR(+) transgene expression to Sertoli cells of gonadotropin-deficient hypogonadal (hpg) mice. Both normal and hpg mouse testes expressed FSHR(+) mRNA. Testis weights of transgenic FSHR(+) hpg mice were increased approximately 2-fold relative to hpg controls (P < 0.02) and contained mature Sertoli cells and postmeiotic germ cells absent in controls, revealing FSHR(+)-initiated autonomous FSH-like testicular activity. Isolated transgenic Sertoli cells had significantly higher basal ( approximately 2-fold) and FSH-stimulated ( approximately 50%) cAMP levels compared with controls, demonstrating constitutive signaling and cell-surface expression of FSHR(+), respectively. Transgenic FSHR(+) also elevated testosterone production in hpg testes, in the absence of circulating LH (or FSH), and it was not expressed functionally on steroidogenic cells, suggesting a paracrine effect mediated by Sertoli cells. The FSHR(+) response was additive with a maximal testosterone dose on hpg testicular development, demonstrating FSHR(+) activity independent of androgen-specific actions. The FSHR(+) response was male specific as ovarian expression of FSHR(+) had no effect on hpg ovary size. These findings reveal transgenic FSHR(+) stimulated a constitutive FSH-like Sertoli cell response in gonadotropin-deficient testes, and pathways that induced LH-independent testicular steroidogenesis. This novel transgenic paradigm provides a unique approach to investigate the in vivo actions of mutated activating gonadotropin receptors.
Mol Endocrinol 2002 Nov
PMID:An activated human follicle-stimulating hormone (FSH) receptor stimulates FSH-like activity in gonadotropin-deficient transgenic mice. 1240 47

The main purpose of the study was to identify the principal gonadal steroids synthesized by male and female sea lampreys, Petromyzon marinus. To achieve this, we used high performance liquid chromatography to separate the steroids in the serum of sexually mature animals, and to separate the steroids produced by gonadal tissue incubated in the presence of radiolabelled precursor steroids, as a means of identifying the major steroidogenic pathways. We were unable to detect evidence of the 'classical' steroids, such as 17beta-estradiol (E(2)) or testosterone (T) in the serum of either male or female lampreys. Instead, the principal chromatographic peaks contained very polar compounds that had elution times consistent with 15alpha-hydroxylated estrogens and androgens, and there were sex-specific differences in the chemical nature and the quantity of these compounds. Testis fragments or ovarian follicles co-incubated with tritium-labelled pregnenolone ([3H]P(5)), 17-hydroxyprogesterone ([3H]17OHP(4)), or androstenedione ([3H]A(4)), provided additional confirmation that the gonads synthesize a range of very polar steroids, and the metabolites found were consistent with the presence of a 15alpha-hydroxylated (15alphaOH) metabolic pathway common to testis and ovary. For ovarian tissue, the major 'end product' metabolites from all three precursors were 15alphaOH-estrogens, and for testis tissue 15alpha-hydroxyprogesterone (15alphaOHP(4)) and 15alpha-hydroxytestosterone (15alphaOHT) and small amounts of 15alphaOH estrogen. Small amounts of E(2) were also produced by both ovarian (all substrates) and testicular tissue (some substrates). Although it was assumed that the E(2) was synthesized via the aromatization of T, [3H]T was not found as an intermediate metabolite. The study suggests that the principal gonadal steroids in sea lamprey are 15alpha-OH compounds, and that only small amounts of E(2) or T are synthesized by the gonads at this stage of reproductive development. There was no direct evidence of progesterone (P(4)) synthesis from [3H]P(5), although the metabolites synthesized by both testis and ovary were indicative of a metabolic pathway that involved P(4) as an intermediate.
Comp Biochem Physiol A Mol Integr Physiol 2003 Feb
PMID:Blood steroid profile and in vitro steroidogenesis by ovarian follicles and testis fragments of adult sea lamprey, Petromyzon marinus. 1254 66

The expression of stage-specific genes during spermatogenesis was determined by isolating two segments of rat seminiferous tubule at different stages of the germinal epithelium cycle delineated by transillumination-delineated microdissection, combined with differential display polymerase chain reaction to identify the differential transcripts formed. A total of 22 cDNAs were identified and accepted by GenBank as new expressed sequence tags. One of the expressed sequence tags was radiolabeled and used as a probe to screen a rat testis cDNA library. A novel full-length cDNA composed of 2228 bp, designated as RSD-3 (rat sperm DNA no.3, GenBank accession no. AF094609) was isolated and characterized. The reading frame encodes a polypeptide consisting of 526 amino acid residues, containing a number of DNA binding motifs and phosphorylation sites for PKC, CK-II, and p34cdc2. Northern blot of mRNA prepared from various tissues of adult rats showed that RSD-3 is expressed only in the testis. The initial expression of the RSD-3 gene was detected in the testis on the 30th postnatal day and attained adult level on the 60th postnatal day. Immunolocalization of RSD-3 in germ cells of rat testis showed that its expression is restricted to primary spermatocytes, undergoing meiosis division I. A human testis homologue of RSD-3 cDNA, designated as HSD-3.1 (GenBank accession no. AF144487) was isolated by screening the Human Testis Rapid-Screen arrayed cDNA library panels by RT-PCR. The exon-intron boundaries of HSD-3.1 gene were determined by aligning the cDNA sequence with the corresponding genome sequence. The cDNA consisted of 12 exons that span approximately 52.8 kb of the genome sequence and was mapped to chromosome 14q31.3.
J Mol Med (Berl) 2003 Jun
PMID:A novel gene, RSD-3/HSD-3.1, encodes a meiotic-related protein expressed in rat and human testis. 1273 79

Testis induction is associated with gonadal Sry and Sox9 expression in mammals, and with Sox9 expression in vertebrates where Sry is absent. In mammals, Sry might initiate testis induction by upregulating Sox9 expression; however, direct evidence supporting this hypothesis is lacking. Models of Sry-negative XX sex reversal (XXSR), in which testes develop in the absence of Sry, could provide the link between Sry and Sox9 in testis induction. To define the stages at which testis determination occurs in the canine model, Sry and Sox9 expression were measured in normal urogenital ridges (UGR) and gonads by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Testicular Sry expression rose continuously during canine developmental ages comparable to human carnegie stages (CS) 16-18, with maximal expression at CS 18. Sox9 was expressed in both male and female canine UGR up to CS 17, at which time testis expression became tenfold greater than in the ovary. Although Sox9 was detected by qRT-PCR in ovaries and mesonephroi of both sexes, expression was detected only in canine testes by whole mount in situ hybridization (WMISH). The timing of Sry and Sox9 expression is consistent with a role in testis determination: Sry expression begins at CS 16 in testes, followed by upregulation of Sox9 expression at CS 17. The quantity and temporal and spatial patterns of Sry and Sox9 expression in normal canine gonads are similar to those in humans, sheep, and pigs. These studies should provide the basis for understanding the mechanism of testis induction in the canine model of Sry-negative XXSR.
Mol Reprod Dev 2003 Aug
PMID:Sry and Sox9 expression during canine gonadal sex determination assayed by quantitative reverse transcription-polymerase chain reaction. 1284 Aug 10


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