Chromosomal Mapping of Five Highly Conserved Murine Homologues of theDrosophilaRING Finger GeneSeven-in-absentia

Holloway, Andrew; Della, Neil G.; Fletcher, Colin; Largespada, David A.; Copeland, Neal G.; Jenkins, Nancy A.; Bowtell, David D.L.

doi:10.1006/geno.1997.4642

Cited by 31 publications

(15 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However GH levels in whole-pituitary lysates from mutant animals were normal (control mice, 22.8 Ϯ 2.1 ng/mg of pituitary tissue [n ϭ 6]; Siah1a Ϫ/Ϫ mice, 18.9 Ϯ 3.7 ng/mg [n ϭ 5]; means Ϯ standard errors of the means). Siah1a maps closely to the proportional dwarf (pdw; [44]) mutation on mouse chromosome 8 (19), but sequencing the Siah1a coding region of pdw mice failed to detect any mutations (data not shown). We have not tested whether pdw is allelic to Siah1a by intercrossing.…”

Section: Vol 22 2002 Meiosis I In Male Mice Requires Siah1a 2295mentioning

confidence: 99%

See 1 more Smart Citation

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

Dickins

Frew

House

et al. 2002

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

The mammalian Siah genes encode highly conserved proteins containing a RING domain. As components of E3 ubiquitin ligase complexes, Siah proteins facilitate the ubiquitination and degradation of diverse protein partners including ␤-catenin, N-CoR, and DCC. We used gene targeting in mice to analyze the function of Siah1a during mammalian development and reveal novel roles in growth, viability, and fertility. Mutant animals have normal weights at term but are postnatally growth retarded, despite normal levels of pituitary growth hormone. Embryonic fibroblasts isolated from mutant animals grow normally. Most animals die before weaning, and few survive beyond 3 months. Serum gonadotropin levels are normal in Siah1a mutant mice; however, females are subfertile and males are sterile due to a block in spermatogenesis. Although spermatocytes in mutant mice display normal meiotic prophase and meiosis I spindle formation, they accumulate at metaphase to telophase of meiosis I and subsequently undergo apoptosis. The requirement of Siah1a for normal progression beyond metaphase I suggests that Siah1a may be part of a novel E3 complex acting late in the first meiotic division.

show abstract

Section: Vol 22 2002 Meiosis I In Male Mice Requires Siah1a 2295mentioning

confidence: 99%

“…The 325-amino-acid Siah2 protein is almost identical to the Siah1 proteins except for a divergent and extended region N-terminal to the RING domain. The human genome contains only two Siah family genes, SIAH1 and SIAH2, encoding proteins almost identical to murine Siah1a and Siah2, respectively (19,20).…”

mentioning

confidence: 99%

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

Dickins

Frew

House

et al. 2002

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Over their C-terminal 250 amino acids, these proteins share more than 85% amino acid identity (Della et al, 1993;Holloway et al, 1997;Hu et al, 1997a;Nemani et al, 1996). Although the function of the mammalian SIAH proteins has not been elucidated, these proteins have been involved in ubiquitin-mediated degradation of their partners such as the receptor for netrin-1 (DCC, deleted in colorectal cancer) and the nuclear receptor corepressor (N-CoR) (Hu et al, 1997b;Zhang et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

SIAH-1 interacts with α-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis

et al. 2000

View full text Add to dashboard Cite

SIAH-1, a human homologue of the Drosophila seven in absentia (Sina), has been implicated in ubiquitinmediated proteolysis of di erent target proteins through its N-terminal RING ®nger domain. SIAH-1 is also induced during p53-mediated apoptosis. Furthermore, SIAH-1-transfected breast cancer cell line MCF-7 exhibits an altered mitotic process resulting in multinucleated giant cells. Now, using the two-hybrid system, we identi®ed two new SIAH interacting proteins: Kid (kinesin like DNA binding protein) and a-tubulin. We demonstrate that SIAH is involved in the degradation of Kid via the ubiquitin ± proteasome pathway. Our results suggest that SIAH-1 but not its N-terminal deletion mutant, a ects the mitosis by an enhanced reduction of kinesin levels. Our results imply, for the ®rst time, SIAH-1 in regulating the degradation of proteins directly implicated in the mitotic process. Oncogene (2000) 19, 5997 ± 6006.

show abstract

“…At a cellular and tissue level, exposure of Siah2 mutants to hypoxia leads to significantly lower protein levels of HIF-1α, resulting in reduced hypoxia-induced gene expression (26). 4 These data suggest a potential for inhibition of the protumorigenic hypoxic response pathway by inhibition of Siah action (Fig. 1).…”

Section: Siah and The Hypoxic Responsementioning

confidence: 92%

Siah Proteins: Novel Drug Targets in the Ras and Hypoxia Pathways

2009

Self Cite

View full text Add to dashboard Cite

The Siah (seven in absentia homolog) family of RING-domain proteins are components of ubiquitin ligase complexes, targeting proteins for proteasomal degradation. Siah family members have been reported to function in Ras, estrogen, DNA-damage, and hypoxia response pathways. Although earlier reports implicated Siah proteins as tumor suppressors, recent studies in mouse models have shown that Siah inhibition impairs tumor growth and metastasis. Given their central role in oncogenic and angiogenic pathways, Siah proteins are attractive novel therapeutic targets in cancer. [Cancer Res 2009;69(23):8835-8]

show abstract

Chromosomal Mapping of Five Highly Conserved Murine Homologues of theDrosophilaRING Finger GeneSeven-in-absentia

Cited by 31 publications

References 34 publications

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

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

SIAH-1 interacts with α-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis

Siah Proteins: Novel Drug Targets in the Ras and Hypoxia Pathways

Contact Info

Product

Resources

About