Potential regulatory relationship between the nested gene DDC8 and its host gene tissue inhibitor of metalloproteinase-2

Jaworski, Diane M.; Beem-Miller, Micah; Lluri, Gentian; Barrantes-Reynolds, Ramiro

doi:10.1152/physiolgenomics.00160.2006

Cited by 23 publications

(25 citation statements)

References 60 publications

(71 reference statements)

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“…For example, the mouse Timp2 hosts BC100451 (DDC8) as a SN gene pair. They are reported to be coexpressed, and even involved in alternative splicing events [45]. The PO gene pair, LRRC49 and THAP10, is silenced by the bidirectional promoter hypermethylation in breast cancer [46].…”

Section: Discussionmentioning

confidence: 99%

A unified framework of overlapping genes: Towards the origination and endogenic regulation

Tsai

Lin

2012

Genomics

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Overlapping genes are pairs of adjacent genes whose genomic regions partially overlap. They are notable by their potential intricate regulation, such as cis-regulation of nested gene-promoter configurations, and post-transcriptional regulation of natural antisense transcripts. The originations and consequent detailed regulation remain obscure. Herein, we propose a unified framework comprising biological classification rules followed by extensive analyses, namely, exon-sharing analysis, a human-mouse conservation study, and transcriptome analysis of hundreds of microarrays and transcriptome sequencing data (mRNA-Seq). We demonstrate that the tail-to-tail architecture would result from sharing functional elements in 3'-untranslated regions (3'-UTRs) of pre-existing genes. Dissimilarly, we illustrate that the other gene overlaps would originate from a new gene arising in a pre-existing gene locus. Interestingly, these types of coupled overlapping genes may influence each other synergistically or competitively during transcription, depending on the promoter configurations. This framework discloses distinctive characteristics of overlapping genes to be a foundation for a further comprehensive understanding of them.

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Section: Discussionmentioning

confidence: 99%

A unified framework of overlapping genes: Towards the origination and endogenic regulation

Tsai

Lin

2012

Genomics

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“…The activity of TIMP-2 that inhibits endothelial cell proliferation was localized to the carboxyterminal domain of TIMP-2, specifically to the carboxyterminal disulfide loop, referred to as loop 6 [52]. It is interesting to note that this region is encoded by exon 5 of the TIMP-2 gene, and as noted above the TIMP-2 deficient mice may produce alternative splice variants of the DDC8 gene that could express proteins containing a TIMP-2 loop 6 structure [20]. This may in part explain the benign phenotype of this knock out mouse strain.…”

Section: Identification Of Non-mmp-dependent Timp Functionsmentioning

confidence: 94%

“…The synapsin-TIMP gene nesting relationship began phylogenetically as far back as Drosophila [18]. A recent report describes a nested gene within the very large (~60 kb) first intron of the TIMP-2 gene [19], known as DDC8 [20]. Furthermore, these authors demonstrate that the brain of the TIMP-2 knock out mouse described by Wang et al contains TIMP-2 mRNA encoding exons 2-5 downstream of DDC8, suggesting alternative splicing between these two genes [20,21].…”

Section: Timps: Mmp Inhibitors and Activatorsmentioning

confidence: 99%

The tumor microenvironment: regulation by MMP-independent effects of tissue inhibitor of metalloproteinases-2

Stetler-Stevenson

2007

Cancer Metastasis Rev

126

115

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Proteolytic remodeling of the extracellular matrix is an important component of disease progression in many chronic disease states and is the initiating event in the formation of the tumor microenvironment in cancer. It is the balance of extracellular matrix degrading enzymes, the matrix metalloproteinases (MMPs) and their endogenous inhibitors that determine the extent of tissue remodeling. Unchecked MMP activity can result in significant tissue damage, facilitate disease progression and is associated with host responses to pathologic injury such as angiogenesis and inflammation. The tissue inhibitors of metalloproteinases (TIMPs) have been shown to regulate MMP activity. However, recent findings demonstrate that the tissue inhibitor of metalloproteinases-2 (TIMP-2) inhibits the mitogenic response of human microvascular endothelial cells to growth factors, such as VEGF-A and FGF-2 in vitro and angiogenesis in vivo. The mechanism of this effect is independent of metalloproteinase inhibition. Our lab is the first to demonstrate a cell-surface signaling receptor for a member of the TIMP family and suggest that TIMP-2 functions to regulate cellular responses to growth factors. These new findings are discussed in terms of a model of TIMP-2 regulation of cellular functions in the tumor microenvironment.

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“…It has similarities to cytoskeletal proteins (Catalano et al, 1997;Iguchi et al, 2006). The Ddc8 gene is nested within the first intron of TIMP-2 [ID: T3-577], which is also expressed in the testis (Grima et al, 1996;Jaworski et al, 2007 (Khatchadourian et al, 2007;Rao et al, 2001). In mice with a generated HIP1r mutant allele, fertility is maintained suggesting that HIP1 or other related members of the clathrin family can compensate.…”

Section: Microscopy Research and Techniquementioning

confidence: 99%

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 3: Developmental changes in spermatid flagellum and cytoplasmic droplet and interaction of sperm with the zona pellucida and egg plasma membrane

Hermo¹,

Pelletier²,

Cyr³

et al. 2009

Microscopy Res & Technique

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Spermiogenesis constitutes the steps involved in the metamorphosis of spermatids into spermatozoa. It involves modification of several organelles in addition to the formation of several structures including the flagellum and cytoplasmic droplet. The flagellum is composed of a neck region and middle, principal, and end pieces. The axoneme composed of nine outer microtubular doublets circularly arranged to form a cylinder around a central pair of microtubules is present throughout the flagellum. The middle and principal pieces each contain specific components such as the mitochondrial sheath and fibrous sheath, respectively, while outer dense fibers are common to both. A plethora of proteins are constituents of each of these structures, with each playing key roles in functions related to the fertility of spermatozoa. At the end of spermiogenesis, a portion of spermatid cytoplasm remains associated with the released spermatozoa, referred to as the cytoplasmic droplet. The latter has as its main feature Golgi saccules, which appear to modify the plasma membrane of spermatozoa as they move down the epididymal duct and hence may be partly involved in male gamete maturation. The end product of spermatogenesis is highly streamlined and motile spermatozoa having a condensed nucleus equipped with an acrosome. Spermatozoa move through the female reproductive tract and eventually penetrate the zona pellucida and bind to the egg plasma membrane. Many proteins have been implicated in the process of fertilization as well as a plethora of proteins involved in the development of spermatids and sperm, and these are high lighted in this review.

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Potential regulatory relationship between the nested gene DDC8 and its host gene tissue inhibitor of metalloproteinase-2

Cited by 23 publications

References 60 publications

A unified framework of overlapping genes: Towards the origination and endogenic regulation

A unified framework of overlapping genes: Towards the origination and endogenic regulation

The tumor microenvironment: regulation by MMP-independent effects of tissue inhibitor of metalloproteinases-2

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 3: Developmental changes in spermatid flagellum and cytoplasmic droplet and interaction of sperm with the zona pellucida and egg plasma membrane

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