Cloning of a New Member of the Insulin Gene Superfamily (INSL4) Expressed in Human Placenta

Chassin, Dorine; Laurent, Anne; Janneau, Jean-Louis; Berger, Roland; Bellet, Dominique

doi:10.1006/geno.1995.9980

Cited by 96 publications

(71 citation statements)

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“…The chromosomal localization of this gene was earlier reported by Chassin et al (1995) to the 9p24 locus by FISH analysis, while the Whitehead Institute maps it to a more precise position to 9p24·1. The localization of these three insulin-related genes within the same chromosomal locus probably reflects their evolutionary relationship.…”

Section: Discussionmentioning

confidence: 75%

Analysis of the 5'-upstream regions of the human relaxin H1 and H2 genes and their chromosomal localization on chromosome 9p24.1 by radiation hybrid and breakpoint mapping

Garibay-Tupas¹,

Csiszár²,

Fox³

et al. 1999

Journal of Molecular Endocrinology

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Relaxins are known endocrine and autocrine/ paracrine hormones that play a major role in reproduction. In the human there are two relaxin genes, H1 and H2 which share 90% sequence homology within their coding region. The biological and evolutionary significance of two highly homologous and biologically active human relaxins is unknown. In order to achieve a better understanding of the regulatory mechanisms involved in the differential expression of these two genes and to gain insight into their role(s) in the preterm premature rupture of the membranes, we have investigated the properties of their 5 -upstream regions and mapped them both by radiation hybrid and breakpoint mapping into the same chromosome 9p24·1 locus. The 5 ends of these relaxin genes could be divided into a proximal highly homologous segment and a distal non-homologous region. Within the proximal region are contained several putative regulatory elements common to both genes, suggesting a similar regulatory mechanism. The clustering of the relaxin genes within the same chromosomal locus suggests that these genes may be under a common regulation. On the other hand, a distinct gene-specific regulation may also exist for the individual relaxin genes since cis elements specific to each gene were identified at their 5 ends. Moreover, the observed divergence at the distal region of their 5 -upstream sequences may provide the structural features that act as gene-specific transcription regulators. Since the two genes are highly homologous in both their coding and flanking regions, the divergence at the distal region of their 5 ends may be important in the regulation of these genes and in their involvement in the pathology of preterm birth.

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Section: Discussionmentioning

confidence: 75%

Analysis of the 5'-upstream regions of the human relaxin H1 and H2 genes and their chromosomal localization on chromosome 9p24.1 by radiation hybrid and breakpoint mapping

Garibay-Tupas¹,

Csiszár²,

Fox³

et al. 1999

Journal of Molecular Endocrinology

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“…Shortly after the discovery of INSL3, a cDNA clone for another member of the relaxin peptide family was identified independently by two groups during screening of cDNA libraries of first-trimester human placenta (Chassin et al, 1995;Koman et al, 1996). The protein product of this gene was named early placenta insulin-like peptide (Chassin et al, 1995) and placentin (Koman et al, 1996), respectively.…”

Section: Brief Historical Background Of Relaxin Family Peptides Anmentioning

confidence: 99%

“…The protein product of this gene was named early placenta insulin-like peptide (Chassin et al, 1995) and placentin (Koman et al, 1996), respectively. The gene has been named insulinlike 4 (INSL4) based on the nomenclature used for the INSL3 gene.…”

Section: Brief Historical Background Of Relaxin Family Peptides Anmentioning

confidence: 99%

International Union of Pharmacology LVII: Recommendations for the Nomenclature of Receptors for Relaxin Family Peptides

Bathgate

Ivell²,

Sanborn³

et al. 2006

Pharmacol Rev

291

256

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“…Insulin superfamily genes are ubiquitous in vertebrates, and have been identified in invertebrates, including insects, molluscs, and the nematode Caenorhabditis elegans (Duret et al 1998;Gregoire et al 1998;Smit et al 1998;Kawano et al 2000). Seven members of the insulin superfamily have been identified in humans, including insulin (Brown et al 1955), insulin-like growth factors (IGFs) I and II (Rinderknecht and Humbel 1978a,b), relaxins HI and HII (Bedarkar et al 1977;Schwabe and McDonald 1977), early placenta insulin-like peptide (EPIL) (Chassin et al 1995;Koman et al 1996), and relaxin-like factor (Bullesbach and Schwabe 1995). These hormones mediate diverse functions.…”

mentioning

confidence: 99%

Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family

Pierce

Costa²,

Wisotzkey³

et al. 2001

Genes Dev.

602

650

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The activity of the DAF-2 insulin-like receptor is required for Caenorhabditis elegans reproductive growth and normal adult life span. Informatic analysis identified 37 C. elegans genes predicted to encode insulin-like peptides. Many of these genes are divergent insulin superfamily members, and many are clustered, indicating recent diversification of the family. The ins genes are primarily expressed in neurons, including sensory neurons, a subset of which are required for reproductive development. Structural predictions and likely C-peptide cleavage sites typical of mammalian insulins suggest that ins-1 is most closely related to insulin. Overexpression of ins-1, or expression of human insulin under the control of ins-1 regulatory sequences, causes partially penetrant arrest at the dauer stage and enhances dauer arrest in weak daf-2 mutants, suggesting that INS-1 and human insulin antagonize DAF-2 insulin-like signaling. A deletion of the ins-1 coding region does not enhance or suppress dauer arrest, indicating a functional redundancy among the 37 ins genes. Of five other ins genes tested, the only other one bearing a predicted C peptide also antagonizes daf-2 signaling, whereas four ins genes without a C peptide do not, indicating functional diversity within the ins family. Insulin and its related proteins define a superfamily of secreted proteins that share a structural motif stabilized by a set of stereotypical disulfide bonds (Blundell and Humbel 1980;Murray-Rust et al. 1992). Insulin superfamily genes are ubiquitous in vertebrates, and have been identified in invertebrates, including insects, molluscs, and the nematode Caenorhabditis elegans (Duret et al. 1998;Gregoire et al. 1998;Smit et al. 1998;Kawano et al. 2000). Seven members of the insulin superfamily have been identified in humans, including insulin (Brown et al. 1955), insulin-like growth factors (IGFs) I and II (Rinderknecht and Humbel 1978a,b), relaxins HI and HII (Bedarkar et al. 1977;Schwabe and McDonald 1977), early placenta insulin-like peptide (EPIL) (Chassin et al. 1995;Koman et al. 1996), and relaxin-like factor (Bullesbach and Schwabe 1995). These hormones mediate diverse functions. Insulin is a metabolic hormone that acts on target tissues to increase glucose uptake and energy storage, IGFs are mitogenic stimulators that control cell survival and proliferation, and relaxin causes dilation of the symphysis pubis before parturition and vasodilation. No function is yet known for either EPIL or relaxin-like factor. Bombyxin in silk moths (Satake et al. 1997), and the neurons that secrete locust and molluscan insulin-related proteins (Smit et al. 1988;Lagueux et al. 1990) regulate metabolism, implicating insulin-like proteins in metabolic control broadly in animal phylogeny. The insulin-like proteins that regulate metabolism, insulin in vertebrates, bombyxin from silk moths, molluscan MIP, and locust LIRP, appear to be processed proteolytically to remove an internal C peptide (Smit et al. 1988;Lagueux et al. 1990;Kondo et al. 1996). This proc...

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Cloning of a New Member of the Insulin Gene Superfamily (INSL4) Expressed in Human Placenta

Cited by 96 publications

References 0 publications

Analysis of the 5'-upstream regions of the human relaxin H1 and H2 genes and their chromosomal localization on chromosome 9p24.1 by radiation hybrid and breakpoint mapping

Analysis of the 5'-upstream regions of the human relaxin H1 and H2 genes and their chromosomal localization on chromosome 9p24.1 by radiation hybrid and breakpoint mapping

International Union of Pharmacology LVII: Recommendations for the Nomenclature of Receptors for Relaxin Family Peptides

Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family

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