The Ubiquitin Ligase Component Siah1a Is Required for Completion of Meiosis I in Male Mice

Dickins, Ross A.; Frew, Ian J.; House, Colin M.; O'Bryan, Moira K; Holloway, Andrew; Haviv, Izhak; Traficante, Nadia; Kretser, David Morritz de; Bowtell, David D.L.

doi:10.1128/mcb.22.7.2294-2303.2002

Cited by 99 publications

(81 citation statements)

References 51 publications

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“…The generation of double knockout animals for the mouse homo- logues of Siah, Siah1a and Siah2, has demonstrated an essential role in embryonic development, whereas the individual knockout phenotypes are less severe (25)(26)(27)(28). Currently, little is known about the regulation of Siah, but it appears that hypoxia, Wnt 5a, and p53 are capable of up-regulating Siah mRNA and protein expression (28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

Estrogen down-regulation of the corepressor N-CoR: Mechanism and implications for estrogen derepression of N-CoR-regulated genes

Frasor

Danes

Funk

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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C ellular activity is precisely regulated by a finely tuned balance between coactivator and corepressor proteins that control transcriptional networks during development and in normal and cancerous states (1). The corepressors N-CoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoid and thyroid hormone receptors) play crucial roles in transcriptional repression by multiple classes of transcription factors, including some nuclear hormone receptors. Repression by N-CoR and SMRT results from their association with large histone deacetylase complexes, which lead to histone deacetylation, altered chromatin structure, and decreased gene transcription (reviewed in ref. 2). Although few studies have demonstrated that N-CoR expression is regulated at the level of gene transcription, several examples of posttranslational regulation of N-CoR expression and activity have been described. Recent studies have shown that N-CoR interaction with transcription factors, such as NF-B and estrogen receptor (ER), can be reduced through translocation of N-CoR out of the nucleus and into the cytoplasm (3-5). N-CoR has also been shown to be regulated by ubiquitin-mediated protein degradation through an interaction with the E3 ubiquitin ligase Siah2, a mammalian homolog of Drosophila seven in absentia (Sina), which leads to the ubiquitination and degradation of N-CoR by the 26S proteasome (6).The majority of estrogen's effects on its numerous target tissues are mediated by its two receptors, ER␣ and ER␤, which act primarily as ligand-dependent transcription factors. Upon binding to its ligand, the ER associates with DNA either directly at estrogen response elements or through tethering to other transcription factors, leading to the recruitment of transcriptional coregulators and chromatin-modifying complexes and the regulation of gene expression (7). We and others (8-17) have used microarray gene expression profiling to identify estrogen target genes in breast cancer cells, where estrogen has been shown to stimulate proliferation and suppress apoptosis through the regulation of multiple genes. These studies have demonstrated that, as expected, estrogen up-regulates many cell-cycle regulators, growth factors, and antiapoptotic genes but also down-regulates a number of cell-cycle inhibitors and proapoptotic genes.Estrogen also regulates the mRNA expression of important transcriptional regulators, both transcription factors and transcriptional coactivators and corepressors (12). Evidence supporting the idea that 17␤-estradiol (E2) is capable of regulating the expression of coregulators has grown in the past few years. For example, this hormone has been shown to up-regulate mRNA levels for the corepressors RIP140 (12, 18), SHP (19), and SHARP (20) and also to down-regulate mRNA levels for the coactivators 21). In addition to the regulation of mRNA for some coregulators, the activity of these proteins can be modulated by hormone by changing the protein's state of phosphorylation, as observed for the coactivator SRC3͞AIB1...

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Section: Discussionmentioning

confidence: 99%

Estrogen down-regulation of the corepressor N-CoR: Mechanism and implications for estrogen derepression of N-CoR-regulated genes

Frasor

Danes

Funk

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Analysis of pachytene spermatocytes in mutant mice showed damaged synaptonemal complexes (Kwon et al, 2003b). Inactivation of the E3 Siah1 also leads to a meiotic defect in which germ cells are unable to progress normally past metaphase I (Dickins et al, 2002). Deubiquitinating enzymes also play a role.…”

Section: Introductionmentioning

confidence: 99%

Regulated expression of the ubiquitin protein ligase, E3^Histone/LASU1/Mule/ARF‐BP1/HUWE1, during spermatogenesis

Liu

Miao

Xia

et al. 2007

Developmental Dynamics

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A ubiquitin protein ligase (E3), E3Histone /LASU1 (Mule/ARF-BP1/HUWE1), was recently identified that mediates ubiquitination of core histones, the Mcl-1 anti-apoptotic protein, and the p53 tumor suppressor protein. However, the expression of E3 Histone /LASU1 remains poorly studied. Because we identified E3 Histone /LASU1 from the testis, we explored its regulation during spermatogenesis. In the first wave of rat spermatogenesis, E3Histone /LASU1 mRNA and protein had peak expression at days 10 and 20, respectively, and decreased with age. Consistent with these findings, immunohistochemistry revealed that E3 Histone /LASU1 was highly expressed in nuclei from spermatogonia to mid-pachytene spermatocytes. There was no obvious staining in spermatids, when histones are ubiquitinated and degraded.

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“…Sae2 is a gene encoding a subunit of sUMo-1 activating enzyme, which is homologous to ubiquitin-activating enzymes [7]. since targeted disruptions of genes associated with the ubiquitin-conjugating enzymes resulted in defects of spermatogenesis in mice [2,8,11] and sUMo proteins were reported to be involved in spermatogenesis [17,25], Sae2 might also have a particular function in spermatogenesis. Rhpn2 encodes rho GTPase-binding protein which regulates cell adhesion, motility, and cytokinesisis.…”

Section: Discussionmentioning

confidence: 99%

Characterization and Linkage Mapping of an ENU-Induced Mutant Mouse with Defective Spermatogenesis

et al. 2009

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repro23 is an autosomal recessive mutation of the mouse generated by the N-ethyl-N-nitrosourea (ENU)-induced mutagenesis program at The Jackson Laboratory. The repro23/repro23 homozygous mouse shows male-specific infertility caused by defective spermatogenesis. In the present study, we investigated the testicular pathology of the affected mouse and performed linkage analysis to determine the chromosomal localization of the repro23 locus. Histological examination of the affected testis showed that the seminiferous epithelium of the repro23/repro23 mice contained spermatogonia and early stage spermatocytes, but no spermatids or spermatozoa. Immunohistochemical staining for Hsc70t, a spermatid specific protein, confirmed the absence of elongating spermatids. These findings indicated interruption of the spermatogenesis during meiosis in the repro23/repro23 mouse. By linkage analysis using 137 affected mice of F 2 progeny obtained from crosses between repro23/repro23 female and JF1/Ms (+/+) male mice, the repro23 locus was mapped to 2.2-Mb region of mouse chromosome 7. Although this region contains several potential candidate genes for the repro23 mutation, no gene already identified as a cause of defective speramatogenesis was in this region. Therefore, the gene responsible for the repro23 mutation is suggested to be a novel gene which plays an essential role in mammalian spermatogenesis.

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The Ubiquitin Ligase Component Siah1a Is Required for Completion of Meiosis I in Male Mice

Cited by 99 publications

References 51 publications

Estrogen down-regulation of the corepressor N-CoR: Mechanism and implications for estrogen derepression of N-CoR-regulated genes

Estrogen down-regulation of the corepressor N-CoR: Mechanism and implications for estrogen derepression of N-CoR-regulated genes

Regulated expression of the ubiquitin protein ligase, E3^Histone/LASU1/Mule/ARF‐BP1/HUWE1, during spermatogenesis

Characterization and Linkage Mapping of an ENU-Induced Mutant Mouse with Defective Spermatogenesis

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The Ubiquitin Ligase Component Siah1a Is Required for Completion of Meiosis I in Male Mice

Cited by 99 publications

References 51 publications

Estrogen down-regulation of the corepressor N-CoR: Mechanism and implications for estrogen derepression of N-CoR-regulated genes

Estrogen down-regulation of the corepressor N-CoR: Mechanism and implications for estrogen derepression of N-CoR-regulated genes

Regulated expression of the ubiquitin protein ligase, E3Histone/LASU1/Mule/ARF‐BP1/HUWE1, during spermatogenesis

Characterization and Linkage Mapping of an ENU-Induced Mutant Mouse with Defective Spermatogenesis

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Regulated expression of the ubiquitin protein ligase, E3^Histone/LASU1/Mule/ARF‐BP1/HUWE1, during spermatogenesis