Gene Expression Analysis of Hematopoietic Progenitor Cells Identifie<i>s Dlg7</i>as a Potential Stem Cell Gene

Gudmundsson, Kristbjorn O.; Thorsteinsson, L.; Sigurjónsson, Ólafur E.; Keller, Jonathan R.; Olafsson, Karl; Egeland, Torstein; Guðmundsson, Sveinn; Rafnar, Thorunn

doi:10.1634/stemcells.2005-0479

Cited by 34 publications

(26 citation statements)

References 49 publications

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“…The Dlg family contains other members, Dlg2 to Dlg7, which may also interact with Gag in T cells. However Dlg3 (SAP102/neuroendocrine-dlg) and Dlg7 are not expressed in T cells (Makino et al, 1997;Gudmundsson et al, 2007). Moreover, a very similar band pattern was observed in immunoblots performed on T cell lysates when using either the anti-PDZ antibody, which recognizes Dlg1 as well as other proteins of the Dlg family, or the Dlg1 specific antibody (data not shown).…”

Section: Discussionmentioning

confidence: 53%

Human Discs Large Is a New Negative Regulator of Human Immunodeficiency Virus-1 Infectivity

Perugi

Muriaux

Ramirez

et al. 2009

MBoC

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Human immunodeficiency virus (HIV)-1 replication is positively or negatively regulated through multiple interactions with host cell proteins. We report here that human Discs Large (Dlg1), a scaffold protein recruited beneath the plasma membrane and involved in the assembly of multiprotein complexes, restricts HIV-1 infectivity. The endogenous Dlg1 and HIV-1 Gag polyprotein spontaneously interact in HIV-1-chronically infected T cells. Depleting endogenous Dlg1 in either adherent cells or T cells does not affect Gag maturation, production, or release, but it enhances the infectivity of progeny viruses five- to sixfold. Conversely, overexpression of Dlg1 reduces virus infectivity by approximately 80%. Higher virus infectivity upon Dlg1 depletion correlates with increased Env content in cells and virions, whereas the amount of virus-associated Gag or genomic RNA remains identical. Dlg1 knockdown is also associated with the redistribution and colocalization of Gag and Env toward CD63 and CD82 positive vesicle-like structures, including structures that seem to still be connected to the plasma membrane. This study identifies both a new negative regulator that targets the very late steps of the HIV-1 life cycle, and an assembly pathway that optimizes HIV-1 infectivity.

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Section: Discussionmentioning

confidence: 53%

Human Discs Large Is a New Negative Regulator of Human Immunodeficiency Virus-1 Infectivity

Perugi

Muriaux

Ramirez

et al. 2009

MBoC

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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%

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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“…DLGAP5 and BUB1B are overexpressed in ACCs. The former is involved in stem cell pluripotency and carcinogenesis (17,18) and the latter controls mitotic checkpoint and chromosomal segregation during mitosis (18,19). PINK1 gene, which is regulated by the PTEN gene and is involved with mitochondrial integrity, was found to be downregulated in ACTs (20).…”

Section: Bub1b-pink1 As a Predictor Of Overall Survival In Accsmentioning

confidence: 99%

Combined expression of BUB1B, DLGAP5, and PINK1 as predictors of poor outcome in adrenocortical tumors: validation in a Brazilian cohort of adult and pediatric patients

Fragoso¹,

Almeida²,

Mazzuco³

et al. 2012

European Journal of Endocrinology

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Background: A recent microarray study identified a set of genes whose combined expression patterns were predictive of poor outcome in a cohort of adult adrenocortical tumors (ACTs). The difference between the expression values measured by qRT-PCR of DLGAP5 and PINK1 genes was the best molecular predictor of recurrence and malignancy. Among the adrenocortical carcinomas, the combined expression of BUB1B and PINK1 genes was the most reliable predictor of overall survival. The prognostic and molecular heterogeneity of ACTs raises the need to study the applicability of these molecular markers in other cohorts. Objective: To validate the combined expression of BUB1B, DLGAP5, and PINK1 as outcome predictor in ACTs from a Brazilian cohort of adult and pediatric patients. Patients and methods: BUB1B, DLGAP5, and PINK1 expression was assessed by quantitative PCR in 53 ACTs from 52 patients -24 pediatric and 28 adults (one pediatric patient presented a bilateral asynchronous ACT). Results: DLGAP5-PINK1 and BUB1B-PINK1 were strong predictors of disease-free survival and overall survival, respectively, among adult patients with ACT. In the pediatric cohort, these molecular predictors were only marginally associated with disease-free survival but not with overall survival. Conclusion: This study confirms the prognostic value of the combined expression of BUB1B, DLGAP5, and PINK1 genes in a Brazilian group of adult ACTs. Among pediatric ACTs, other molecular predictors of outcome are required.

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Gene Expression Analysis of Hematopoietic Progenitor Cells Identifies Dlg7as a Potential Stem Cell Gene

Cited by 34 publications

References 49 publications

Human Discs Large Is a New Negative Regulator of Human Immunodeficiency Virus-1 Infectivity

Human Discs Large Is a New Negative Regulator of Human Immunodeficiency Virus-1 Infectivity

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

Combined expression of BUB1B, DLGAP5, and PINK1 as predictors of poor outcome in adrenocortical tumors: validation in a Brazilian cohort of adult and pediatric patients

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