Isolation and characterization of a novel gene encoding nuclear protein at a locus (<i>D11S636</i>) tightly linked to multiple endocrine neoplasia type 1 (MEN1)

Toda, Takayoshi; Iida, Aritoshi; Miwa, Tokiko; Nakamura, Yusuke; Imai, Takashi

doi:10.1093/hmg/3.3.465

Cited by 48 publications

(37 citation statements)

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“…Two other proteins also show significant similarity to GLD-1, Sam68, and GRP33 (see Fig. 4): A predicted protein from C. elegans, BO280.11 (Wilson et al 1994), and ZFM1 from humans (Toda et al 1994). We confirmed that a gene is transcribed from the BO280.11 region by isolating and sequencing cDNA clones (see Materials and methods).…”

Section: Conserved Domains In the Gld-1 Predicted Proteinmentioning

confidence: 55%

“…This small region, which we refer to as the CGA region, is just carboxy-terminal to the GSG domain and apparently not found in Sam68 and GRP33. This region, as well as a partial GSG domain, is also found in ZFM 1, a gene that is tightly linked to multiple endocrine neoplasia type 1 (MEN1) in humans (Toda et al 1994). Like the GSG domain, the CGA region is important for GLD-I function, as several gld-1 mutations affect it (refer to Table 1; and Fig.…”

Section: Gld-1 Has a Tumor Suppressor Function In Vivomentioning

confidence: 97%

“…Both alleles produce abnormal oocytes and behave as partial loss-of-function mutations with respect to oogenesis (Francis et al 1995a). The class E (Wong et al 1992), ZFM1 (Toda et al 1994), BO280.1 lb (see Materials and methods), and GLD-1 (Fig. 3).…”

Section: Molecular Analysis Of Gld-1 Mutations That Affect Oogenesismentioning

confidence: 99%

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Mutations in gld-1, a female germ cell-specific tumor suppressor gene in Caenorhabditis elegans, affect a conserved domain also found in Src-associated protein Sam68.

Jones¹,

Schedl²

1995

Genes Dev.

245

223

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The gld-1 gene of Caenorhabditis elegans is a germ-line-specific tumor suppressor gene that is essential for oogenesis. We have cloned the gld-1 gene and find that it encodes two proteins that differ by 3 amino acids.The predicted proteins contain a -170-amino-acid region that we term the GSG domain (GRP33/Sam68/GLD-1), on the basis of significant similarity between GLD-1, GRP33 from shrimp, and the Src-associated protein Sam68 from mouse (also described as GAPap62 An important contribution to our understanding of cancer biology has been the identification of tumor suppressor genes in which loss of gene function is a factor in tumor formation. A number of tumor suppressor genes are involved in the cell cycle (for recent review, see Hartwell and Kastan 1994). These include cell cycle checkpoint genes (e.g., p53} and DNA repair genes (e.g., MSH2). Other tumor suppressor genes, possibly including WT1 (Kreidberg et al. 1993}, appear to be tied to development, acting in cell type specification or developmental aspects of cell cycle control. Two recent reports describe genetic studies of gld-1, a tumor suppressor gene that is required for normal oocyte development in the nematode Caenorhabditis elegans (Francis et al. 1995a, b). In wild-type C. elegans, diploid animals with a single X chromosome develop as males that make only sperm, whereas diploids with two X chromosomes are hermaphrodites that produce some sperm before switching to the production of oocytes (Fig.

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Section: Conserved Domains In the Gld-1 Predicted Proteinmentioning

confidence: 55%

Section: Gld-1 Has a Tumor Suppressor Function In Vivomentioning

confidence: 97%

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Mutations in gld-1, a female germ cell-specific tumor suppressor gene in Caenorhabditis elegans, affect a conserved domain also found in Src-associated protein Sam68.

Jones¹,

Schedl²

1995

Genes Dev.

245

223

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“…Alignment of the KH domains (16,25) reveals a subfamily of KH-domain-containing proteins including human and murine Sam68 (29,45), Artemia salina GRP33 (6), C. elegans GLD-1 (19), mouse Qk1 (9), human ZFM1 (38), and predicted protein BO280.11b from C. elegans (44). Most recently, two additional members have been identified, including the mammalian splicing factor SF1 (1) and the Drosophila "held-out wings" gene product (GenBank accession no.…”

mentioning

confidence: 99%

Self-Association of the Single-KH-Domain Family Members Sam68, GRP33, GLD-1, and Qk1: Role of the KH Domain

Chen

Damaj

Herrera

et al. 1997

Molecular and Cellular Biology

179

235

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Sam68 is a member of a growing family of proteins that contain a single KH domain embedded in a larger conserved domain of ϳ170 amino acids. Loops 1 and 4 of this KH domain family are longer than the corresponding loops in other KH domains and contain conserved residues. KH domains are protein motifs that are involved in RNA binding and are often present in multiple copies. Here we demonstrate by coimmunoprecipitation studies that Sam68 self-associated and that cellular RNA was required for the association. Deletion studies demonstrated that the Sam68 KH domain loops 1 and 4 were required for self-association. The Sam68 interaction was also observed in Saccharomyces cerevisiae by the two-hybrid system. In situ chemical cross-linking studies in mammalian cells demonstrated that Sam68 oligomerized in vivo. These Sam68 complexes bound homopolymeric RNA and the SH3 domains of p59 fyn and phospholipase C␥1 in vitro, demonstrating that Sam68 associates with RNA and signaling molecules as a multimer. The formation of the Sam68 complex was inhibited by p59 fyn , suggesting that tyrosine phosphorylation regulates Sam68 oligomerization. Other Sam68 family members including Artemia salina GRP33, Caenorhabditis elegans GLD-1, and mouse Qk1 also oligomerized. In addition, Sam68, GRP33, GLD-1, and Qk1 associated with other KH domain proteins such as Bicaudal C. These observations indicate that the single KH domain found in the Sam68 family, in addition to mediating protein-RNA interactions, mediates protein-protein interactions.

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“…At present only two genes, ZFM1 (Toda et al 1994) and FAU1 (Kas et al 1993a), have been assigned to the minimal MEN1 interval, PYGM-D11S449 . Both genes have been excluded as candidates for MEN 1 based on mutation analysis (Kas et al 1993b;Courseaux et al 1996).…”

mentioning

confidence: 99%

A Transcript Map for the 2.8-Mb Region Containing the Multiple Endocrine Neoplasia Type 1 Locus

et al. 1997

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Multiple endocrine neoplasia type 1 (MEN 1) is an inherited cancer syndrome in which affected individuals develop multiple parathyroid, enteropancreatic, and pituitary tumors. The locus for MEN1 is tightly linked to the marker PYGM on chromosome 11q13, and linkage analysis places the MEN1 gene within a 2-Mb interval flanked by the markers D11S1883 and D11S449. Loss of heterozygosity studies in MEN 1 and sporadic tumors suggest that theMEN1 gene encodes a tumor suppressor and have helped to narrow the location of the gene to a 600-kb interval between PYGM andD11S449. Focusing on this smaller MEN1 interval, we have identified and mapped 12 transcripts to this 600-kb region. A precise ordered map of 33 transcripts, including 12 genes known to map to this region, was generated for the 2.8-Mb D11S480–D11S913interval. Fifteen candidate genes (of which 10 were examined exhaustively) were evaluated by Southern blot and/or dideoxy fingerprinting analysis to identify the gene harboring disease-causing mutations.[The sequence data described in this paper have been submitted to GenBank under accession nos. EST06996, U93236,AF001540–AF001547, AF001433–AF001436, AF001891–AF001893,N55476, R19205, and W37647 (see Table 1 for listing of transcripts). The BAC clone sequences have been submitted to GenBank under accession nos. AC000134, AC000159, and AC000353.]

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Isolation and characterization of a novel gene encoding nuclear protein at a locus (D11S636) tightly linked to multiple endocrine neoplasia type 1 (MEN1)

Cited by 48 publications

References 0 publications

Mutations in gld-1, a female germ cell-specific tumor suppressor gene in Caenorhabditis elegans, affect a conserved domain also found in Src-associated protein Sam68.

Mutations in gld-1, a female germ cell-specific tumor suppressor gene in Caenorhabditis elegans, affect a conserved domain also found in Src-associated protein Sam68.

Self-Association of the Single-KH-Domain Family Members Sam68, GRP33, GLD-1, and Qk1: Role of the KH Domain

A Transcript Map for the 2.8-Mb Region Containing the Multiple Endocrine Neoplasia Type 1 Locus

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