Characterization of a Novel Human Cell-Cycle-Regulated Homologue of Drosophila dlg1

Bassal, Sahar; Nomura, Nobuo; Venter, Deon J.; Brand, Karl; McKay, Michael J.; Spek, Peter J. van der

doi:10.1006/geno.2001.6570

Cited by 30 publications

(30 citation statements)

References 17 publications

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“…Also known as discs large homolog 7 or disks large-associated protein 5 [25,26] , HURP was previously thought to represent a stem cell marker as this protein is not detected in fully differentiated cells [27] . Previous reports indicate that HURP overexpression in differentiated cells blocks apoptosis and increases cell growth in response to serum starvation [24,28] .…”

Section: Hurp As a Marker In Hccmentioning

confidence: 99%

“…Aurora-A thus phosphorylates HURP and this process may represent a cellular mechanism that controls mitotic spindle assembly and functions [32] . Therefore, HURP is implicated in stem cell functions [25][26][27] and carcinogenesis in cancer cells of human origins [24,28] . Analysis of gene expression showed that HURP represents a marker of cancer prognosis that can be used to distinguish between benign and malignant adrenocortical tumors [33,34] .…”

Section: Hurp As a Marker In Hccmentioning

confidence: 99%

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Inhibition of apoptosis by oncogenic hepatitis B virus X protein: Implications for the treatment of hepatocellular carcinoma

Chao¹

2016

WJH

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Hepatitis B virus X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). In addition, hepatoma upregulated protein (HURP) is a cellular oncogene that is upregulated in a majority of HCC cases. We highlight here recent findings demonstrating a link between HBx, HURP and anti-apoptosis effects observed in cisplatin-treated HCC cells. We observed that Hep3B cells overexpressing HBx display increased HURP mRNA and protein levels, and show resistance to cisplatin-induced apoptosis. Knockdown of HURP in HBx-expressing cells reverses this effect, and sensitizes cells to cisplatin. The anti-apoptotic effect of HBx requires activation of the p38/MAPK pathway as well as expression of SATB1, survivin and HURP. Furthermore, silencing of HURP using short-hairpin RNA promotes accumulation of p53 and reduces cell proliferation in SK-Hep-1 cells (p53 +/-), whereas these effects are not observed in p53-mutant Mahlavu cells. Similarly, HURP silencing does not affect the proliferation of H1299 lung carcinoma cells or Hep3B HCC cells which lack p53. Silencing of HURP sensitizes SK-Hep-1 cells to cisplatin. While HURP overexpression promotes p53 ubiquitination and degradation by the proteasome, HURP silencing reverses these effects. Inoculation of SK-Hep-1 cancer cells in which HURP has been silenced produces smaller tumors than control in nude mice. Besides, gankyrin, a positive regulator of the E3 ubiquitin ligase MDM2, is upregulated following HURP expression, and silencing of gankyrin reduces HURP-mediated downregulation of p53. In addition, we observed a positive correlation between HURP and gankyrin protein levels in HCC patients (r 2 = 0.778; n = 9). These findings suggest a role for the viral protein HBx and the host protein HURP in preventing p53-mediated apoptosis during cancer progression and establishment of chemoresistance. Core tip: Hepatitis B virus X protein (HBx) plays a critical role in the development of hepatocellular carcinoma (HCC). Hepatoma upregulated protein (HURP) is an oncogene that is upregulated in a majority of HCC cases. However, the role of these proteins in the response of HCC cells to chemotherapeutic drugs remains unclear. We show here that the HBx/SATB1/HURP axis plays a critical role in down-regulating p53 and upregulating anti-apoptotic proteins in vitro and in vivo . We discuss the regulation of this novel pathway and its implications in resistance of HCC cells to chemotherapy.Chao CCK. Inhibition of apoptosis by oncogenic hepatitis B virus X protein: Implications for the treatment of hepatocellular carcinoma.

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Section: Hurp As a Marker In Hccmentioning

confidence: 99%

Section: Hurp As a Marker In Hccmentioning

confidence: 99%

Inhibition of apoptosis by oncogenic hepatitis B virus X protein: Implications for the treatment of hepatocellular carcinoma

Chao¹

2016

WJH

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“…During the preparation of this manuscript, a novel protein KIAA0008 was reported (Bassal et al, 2001). KIAA0008 lacks the first two exons when compared to the HURP gene sequence on chromosome 14 and hence resulted in a product shorter by 81 amino-acid residues at the N-terminus of the coding region (Figure 2a).…”

Section: Note Added In Proofmentioning

confidence: 99%

Identification of a novel cell cycle regulated gene, HURP, overexpressed in human hepatocellular carcinoma

Tsou¹,

Yang²,

et al. 2003

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An analytic strategy was followed to identify putative regulatory genes during the development of human hepatocellular carcinoma (HCC). This strategy employed a bioinformatics analysis that used a database search to identify genes, which are differentially expressed in human HCC and are also under cell cycle regulation. A novel cell cycle regulated gene (HURP) that is overexpressed in HCC was identified. Full-length cDNAs encoding the human and mouse HURP genes were isolated. They share 72 and 61% identity at the nucleotide level and aminoacid level, respectively. Endogenous levels of HURP mRNA were found to be tightly regulated during cell cycle progression as illustrated by its elevated expression in the G 2 /M phase of synchronized HeLa cells and in regenerating mouse liver after partial hepatectomy. Immunofluorescence studies revealed that hepatoma up-regulated protein (HURP) localizes to the spindle poles during mitosis. Overexpression of HURP in 293T cells resulted in an enhanced cell growth at low serum levels and at polyhema-based, anchorage-independent growth assay. Taken together, these results strongly suggest that HURP is a potential novel cell cycle regulator that may play a role in the carcinogenesis of human cancer cells.

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“…Using a cDNA array of 9,180 genes, we identified 153 candidate genes when HCC specimens with and without metastasis were compared and the KIAA0008 gene was one of the leading genes . Up to now, the function of this gene, particularly in the development and progression of cancer, has remained unknown (Bassal et al 2001). To address this issue, we examined the expression of KIAA0008 mRNA in the resected HCC specimens with different invasiveness potentials, and in a series of HCC cell lines with identical genetic background but different invasiveness potential.…”

Section: Introductionmentioning

confidence: 99%

KIAA0008 gene is associated with invasive phenotype of human hepatocellular carcinoma?a functional analysis

Lei

Qin

et al. 2004

J Cancer Res Clin Oncol

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Characterization of a Novel Human Cell-Cycle-Regulated Homologue of Drosophila dlg1

Cited by 30 publications

References 17 publications

Inhibition of apoptosis by oncogenic hepatitis B virus X protein: Implications for the treatment of hepatocellular carcinoma

Inhibition of apoptosis by oncogenic hepatitis B virus X protein: Implications for the treatment of hepatocellular carcinoma

Identification of a novel cell cycle regulated gene, HURP, overexpressed in human hepatocellular carcinoma

KIAA0008 gene is associated with invasive phenotype of human hepatocellular carcinoma?a functional analysis

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