A Novel Human Gene Encoding HECT Domain and RCC1-like Repeats Interacts with Cyclins and Is Potentially Regulated by the Tumor Suppressor Proteins

Mitsui, Kiyofumi; Nakanishi, Makoto; Ohtsuka, Satoshi; Norwood, Thomas H.; Okabayashi, Ken; Miyamoto, Chikara; Tanaka, Keiji; Yoshimura, Akihiko; Ohtsubo, Motoaki

doi:10.1006/bbrc.1999.1777

Cited by 47 publications

(57 citation statements)

References 44 publications

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“…The tumor suppressor, p53, was postulated as a potential mediator for the regulation of the ISGylation system by androgens (Mitsui et al, 1999;Liu et al, 2004), as (i) AR activation inhibits p53 accumulation in the nucleus (Nantermet et al, 2004) and (ii) p53 was transcriptionally downregulated in LNCaP cells by androgens (Supplementary information 6). By the …”

Section: Resultsmentioning

confidence: 99%

“…The Herc5-mediated upregulation by androgens seems to be because of an indirect mechanism of androgen action as no androgen-responsive elements were predicted in a 2000 bp region upstream from the transcription start and within the gene. Interestingly, functional p53 caused a decreased Herc5 expression (Mitsui et al, 1999), which suggested that p53 represents a potential factor for Herc5 upregulation by the nuclear exclusion of p53 in the presence of androgens.…”

Section: Discussionmentioning

confidence: 99%

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Expression, regulation and function of the ISGylation system in prostate cancer

et al. 2009

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The androgen receptor (AR) plays a crucial role in the modulation of prostate cell proliferation and is involved in the development and progression of prostate cancer (PCa). An understanding of the complex regulation of AR provides novel treatment options for PCa. Here, we show (i) that the ubiquitin-like modifier, interferon-stimulated gene 15 (ISG15), and most enzymes involved in ISG15 conjugation were upregulated in tumor samples versus in non-malignant tissues of PCa patients and (ii) that the expression of these components significantly differed between tumors in patients treated with and without androgen ablation. Using PCa cell lines as in vitro models, the specific androgen-mediated, ARdependent regulation of the ISGylation components was confirmed. In addition, the ISGylation system controls AR mRNA and protein expressions, as overexpression of Ube1L as a limiting ISGylation factor in the AR þ androgensensitive PCa cell line, LNCaP, results in significant AR upregulation, accompanied by an increased proliferation even under androgen deprivation. Accordingly, Ube1L knockdown decreased the AR expression. Thus, this study describes for the first time the modulation of AR expression by ISGylation components, which affects the proliferation of PCa cells, thereby providing evidence for a novel function of the ISGylation system in malignant transformation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Expression, regulation and function of the ISGylation system in prostate cancer

et al. 2009

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“…Many of these were already recognized to be associated with cancer, such as DHX9, which inhibits BRCA1 (36); PTMA, which prevents apoptosis (37); CEB1, which is elevated when the function of p53 and RB are compromised (38); GAGED2, which is overexpressed in a variety of tumors (39); STEAP, which is associated with prostate cancer and tumor progression (40); GNB2L1͞RACK1, which inhibits apoptosis (41); PPIA, which is associated with prostate cancer (42); and TPT1, which is overexpressed in colon cancer (43). Some other genes, like OBTP, have no known function.…”

Section: Sage Librarymentioning

confidence: 99%

Gene expression profiles of epithelial cells microscopically isolated from a breast-invasive ductal carcinoma and a nodal metastasis

Zucchi

Mento

Kuznetsov

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Expression profiles of breast carcinomas are difficult to interpret when they are obtained from tissue in toto, which may contain a large proportion of non-cancer cells. To avoid this problem, we microscopically isolated cells from a primary invasive ductal carcinoma of the breast and from an axillary node harboring a metastatic breast carcinoma, to obtain pure populations of carcinoma cells (Ϸ500) and used them for serial analysis of gene expression. The expression profiles generated from both populations of cells were compared with the profile of a disease-free mammary epithelium. We showed that the expression profiles obtained are exclusive of carcinoma cells with no contribution of non-epithelial cells. From a total of 16,939 unique tags analyzed, we detected 559 statistically significant changes in gene expression; some of these genes have not been previously associated with breast cancer. We observed that many of the down-regulated genes are the same in both cancers, whereas the up-regulated genes are completely different, suggesting that the down-regulation of a set of genes may be the basic mechanism of cancer formation, while the up-regulation may characterize and possibly control the state of evolution of individual cancers. The results obtained may help in characterizing the neoplastic process of breast cancer.breast cancer ͉ serial analysis of gene expression ͉ cell microdissection ͉ carcinoma

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“…Members of the HECT family containing an RLD are designated HERC (HECT and RCC1 domain proteins). The clone identified by us, initially termed Croco (GenBank accession number AY337518), is very similar to the cyclin E binding protein 1 (Ceb1) (Mitsui et al, 1999) and was classified as HERC5 according to human genome approved nomenclature. The two sequences differ by a one base pair deletion in the 5′-UTR, by an additional 40 bp at the 5′-UTR of Croco, and five point mutations resulting in exchange of four amino acids.…”

Section: Identification and Cloning Of Herc5mentioning

confidence: 99%

HERC5, a HECT E3 ubiquitin ligase tightly regulated in LPS activated endothelial cells

Kroismayr

Baranyi

Stehlik

et al. 2004

Journal of Cell Science

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By differential screening we isolated genes upregulated in inflammatory cytokine-stimulated human skin microvascular endothelial cells. One of these cDNAs encoded RCC1 (regulator of chromosome condensation 1)-like repeats and a HECT (homologous to E6-AP C-terminus) domain, representing a member of the HERC (HECT and RCC1 domain protein) family of ubiquitin ligases. The mRNA level of this member, HERC5, is specifically upregulated in endothelial cells by the pro-inflammatory cytokines tumor necrosis factor α and interleukin 1β, and by lipopolysaccharide (LPS), but is hardly expressed in other cells of the vascular wall such as primary smooth muscle cells and fibroblasts. Regulation of HERC5 gene expression suggests a critical role for the transcription factor NF-κB. In contrast to mRNA expression HERC5 protein is subject of enhanced degradation upon LPS stimulation of endothelial cells. The time course of LPS-induced changes in HERC5 protein and mRNA levels suggests that the initial drop in HERC5 protein is balanced by increased protein synthesis due to upregulation of HERC5 mRNA. This leads to recovery of HERC5 protein levels within 12 hours of LPS stimulation and points at a tight control of HERC5 protein. To analyze functional activity of this putative member of the ubiquitin-conjugating pathway we performed in vitro assays with different ubiquitin-conjugating enzymes. We found that HERC5 possesses ubiquitin ligase activity and requires the presence of the ubiquitin-conjugating enzyme UbcH5a for its activity. These data show for the first time that a functionally active HECT ubiquitin ligase exhibits a tightly controlled cytosolic level under inflammatory conditions in endothelial cells.

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A Novel Human Gene Encoding HECT Domain and RCC1-like Repeats Interacts with Cyclins and Is Potentially Regulated by the Tumor Suppressor Proteins

Cited by 47 publications

References 44 publications

Expression, regulation and function of the ISGylation system in prostate cancer

Expression, regulation and function of the ISGylation system in prostate cancer

Gene expression profiles of epithelial cells microscopically isolated from a breast-invasive ductal carcinoma and a nodal metastasis

HERC5, a HECT E3 ubiquitin ligase tightly regulated in LPS activated endothelial cells

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