Abundant expression of Dec1/stra13/sharp2 in colon carcinoma: its antagonizing role in serum deprivation-induced apoptosis and selective inhibition of procaspase activation

Li, Yuxin; Zhang, He; Xie, Mingxing; Hu, Maowen; Ge, Shujun; Yang, Dongfang; Wan, Yinsheng; Yan, Bingfang

doi:10.1042/bj20020514

Cited by 101 publications

(147 citation statements)

References 42 publications

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“…Cells that lack the functional tumor suppressor VHL (von Hippel-Lindau) express higher levels of DEC1 (24). Forced expression of DEC1 antagonizes serum deprivation-induced apoptosis and selectively inhibits the activation of procaspases (23). These findings suggest that overexpression of DEC1 provides cells with an unusual survival mechanism and thus is oncogenic.…”

mentioning

confidence: 74%

“…Plasmid-A cDNA encoding the full-length DEC1 was isolated by a cDNA-trapping method (23,26). Several DEC1 mutant constructs were prepared by PCR with the full-length DEC1 as the template.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we and other investigators have recently demonstrated that deregulated cell survival by DEC1 may have oncogenic significance. In paired samples, DEC1 is abundantly expressed in colon carcinomas but not in the adjacent normal tissues (23). High levels of DEC1 transcript are also detected in an array of cancer cell lines derived from a wide range of organs (24).…”

mentioning

confidence: 91%

“…The anti-DEC1 antibody against the COOH-terminal peptide was described elsewhere (23). Protein concentration was deter-mined with BCA assay (Pierce) with bovine serum albumin as the standard.…”

Section: Methodsmentioning

confidence: 99%

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DEC1 Negatively Regulates the Expression of DEC2 through Binding to the E-box in the Proximal Promoter

Xie

Song

et al. 2003

Journal of Biological Chemistry

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Human DEC (differentially expressed in chondrocytes), mouse STRA (stimulated with retinoic acid), and rat SHARP (split and hairy related protein) proteins constitute a new and structurally distinct class of the basic helix-loop-helix proteins. In each species, two members are identified with a sequence identity of >90% in the basic helix-loop-helix region and ϳ40% in the total proteins, respectively. Recently, we have reported that DEC1 is abundantly expressed in colon carcinomas but not in the adjacent normal tissues. The present study was undertaken to extend the expression study of DEC1 and to determine whether DEC1 and DEC2 had similar expression patterns among paired cancer-normal tissues from the colon, lung, and kidney. Without exceptions, DEC1 was markedly higher in the carcinomas, whereas the opposite was true with DEC2. In stable transfectants, tetracycline-induced expression of DEC1 caused proportional decreases in the expression of DEC2. Co-transfection with DEC1 repressed the activity of a DEC2 promoter reporter by as much as 90%. The repression was observed with wild type DEC1 but not its DNA binding-defective mutants. Studies with deletion and site-directed mutants located, in the proximal promoter, an E-box motif that supported the DEC1-mediated repression. Disruption of this E-box markedly abolished the ability of the reporter to respond to DEC1. Our findings assign for DEC1 the first target gene that is regulated through direct DNA binding. DEC/STRA/ SHARP proteins are highly identical in the DNA binding domain but much more diverse in other areas. DEC1-mediated repression on the expression of DEC2 provides an important mechanism that these transcription factors regulate the cellular function not only by modulating the expression of their target genes but also the expression of members within the same class.The basic helix-loop-helix (bHLH) 1 proteins are intimately associated with developmental events such as cell differentiation and lineage commitment (1-6). The HLH domain in the bHLH motif is responsible for dimerization, whereas the basic region mediates DNA binding (1). Based on sequence alignment and domain analysis, human DEC (differentially expressed in chondrocytes), mouse STRA (stimulated with retinoic acid), and rat SHARP (split and hairy related protein) constitute a new and structurally distinct class of bHLH proteins (7-10). These proteins are distantly related to Drosophila Hairy and E(spl) as well as the mammalian homologues (e.g. HES) with the highest sequence identity (ϳ40%) in the bHLH region (1,11,12). Like Hairy/E(spl)/Hes, DEC/STRA/SHARPs contain an orange domain and a proline residue in the DNA binding domain. However, the proline is located 2 residues more toward the NH 2 terminus (1, 8). Another major structural difference on the functional domains is that DEC/STRA/ SHARPs, unlike Hairy/E(Spl)/Hes proteins, lack the COOHterminal WRPW tetrapeptide motif (13). Through this sequence, Hairy/E(spl)/Hes recruit corepressor Groucho to the transcription regulatory complex (13)....

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mentioning

confidence: 74%

“…Plasmid-A cDNA encoding the full-length DEC1 was isolated by a cDNA-trapping method (23,26). Several DEC1 mutant constructs were prepared by PCR with the full-length DEC1 as the template.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

DEC1 Negatively Regulates the Expression of DEC2 through Binding to the E-box in the Proximal Promoter

Xie

Song

et al. 2003

Journal of Biological Chemistry

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126

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“…32,33 It has also various roles in cell proliferation, apoptosis, differentiation, carcinogenesis, cellular metabolism, circadian rhythms, immune regulation and functions as a hypoxia inducible gene as well. [34][35][36][37][38] PLOD2-procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2…”

Section: Hpa028921mentioning

confidence: 99%

Novel signatures of cancer‐associated fibroblasts

Bozóky

Savchenko

Csermely

et al. 2013

Intl Journal of Cancer

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Increasing evidence indicates the importance of the tumor microenvironment, in particular cancer-associated fibroblasts, in cancer development and progression. In our study, we developed a novel, visually based method to identify new immunohistochemical signatures of these fibroblasts. The method employed a protein list based on 759 protein products of genes identified by RNA profiling from our previous study, comparing fibroblasts with differential growth-modulating effect on human cancers cells, and their first neighbors in the human protein interactome. These 2,654 proteins were analyzed in the Human Protein Atlas online database by comparing their immunohistochemical expression patterns in normal versus tumor-associated fibroblasts. Twelve new proteins differentially expressed in cancer-associated fibroblasts were identified (DLG1, BHLHE40, ROCK2, RAB31, AZI2, PKM2, ARHGAP31, ARHGAP26, ITCH, EGLN1, RNF19A and PLOD2), four of them can be connected to the Rho kinase signaling pathway. They were further analyzed in several additional tumor stromata and revealed that the majority showed congruence among the different tumors. Many of them were also positive in normal myofibroblast-like cells. The new signatures can be useful in immunohistochemical analysis of different tumor stromata and may also give us an insight into the pathways activated in them in their true in vivo context. The method itself could be used for other similar analysis to identify proteins expressed in other cell types in tumors and their surrounding microenvironment.

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Dynamic regulation of the Stra13/Sharp/Dec bHLH repressors in mammary epithelium

St-Pierre

Cooper

Jiang

et al. 2004

Developmental Dynamics

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Mammary gland development is a dynamic process involving cyclical proliferation, cellular differentiation, and cell death. In this study, we have determined that expression of the Stra13/Sharp/Dec basic helix-loop-helix (bHLH) family is dynamically regulated in mammary epithelium. In cultured HC11 cells, epidermal growth factor (EGF) treatment rapidly induces Stra13 protein accumulation, which is blocked by the synthetic glucocorticoid, dexamethasone. Neither the induction of Stra13 by EGF nor its repression by dexamethasone correlates with changes in Stra13 mRNA levels. During mouse mammary gland development in vivo, Stra13 is highly expressed in epithelial ducts during puberty, and strongly induced in both ducts and alveoli during early involution, while the related Sharp-1 gene is highly expressed only during late stages of involution. Together, these data indicate that Stra13/Dec/Sharp-family bHLH repressors are dynamically regulated during mammary gland development and may function to regulate apoptosis in this tissue. Developmental Dynamics 230:124 -130, 2004.

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Abundant expression of Dec1/stra13/sharp2 in colon carcinoma: its antagonizing role in serum deprivation-induced apoptosis and selective inhibition of procaspase activation

Cited by 101 publications

References 42 publications

DEC1 Negatively Regulates the Expression of DEC2 through Binding to the E-box in the Proximal Promoter

DEC1 Negatively Regulates the Expression of DEC2 through Binding to the E-box in the Proximal Promoter

Novel signatures of cancer‐associated fibroblasts

Dynamic regulation of the Stra13/Sharp/Dec bHLH repressors in mammary epithelium

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