Short mitochondrial ARF triggers Parkin/PINK1-dependent mitophagy.

Parkinson disease (PD) is a complex neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra. Multiple genes have been associated with PD, including Parkin and PINK1. Recent studies have established that the Parkin and PINK1 proteins function in a common mitochondrial quality control pathway, whereby disruption of the mitochondrial membrane potential leads to PINK1 stabilization at the mitochondrial outer surface.

Characterization of Wnt2 overexpression in a rat granulosa cell line (DC3): effects on CTNNB1 activation.

WNTs comprise a family of secreted glycoproteins that are essential for normal embryonic development of the female reproductive system. The functional role that WNTs play in the postnatal ovary is poorly defined. We have shown previously that Wnt2 and Fzd4 mRNAs are expressed in granulosa cells of the postnatal rat ovary.

Ataxin-3 deubiquitination is coupled to Parkin ubiquitination via E2 ubiquitin-conjugating enzyme.

We reported previously that parkin, a Parkinson disease-associated E3 ubiquitin-ligase interacts with ataxin-3, a deubiquitinating enzyme associated with Machado-Joseph disease. Ataxin-3 was found to counteract parkin self-ubiquitination both in vitro and in cells. Moreover, ataxin-3-dependent deubiquitination of parkin required the catalytic cysteine 14 in ataxin-3, although the precise mechanism remained unclear.

The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability.

Machado-Joseph disease (MJD), the most common dominantly inherited ataxia worldwide, is caused by a polyglutamine (polyQ) expansion in the deubiquitinating (DUB) enzyme ataxin-3. Interestingly, MJD can present clinically with features of Parkinsonism. In this study, we identify parkin, an E3 ubiquitin-ligase responsible for a common familial form of Parkinson's disease, as a novel ataxin-3 binding partner.

Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels.

Mutations in the parkin gene result in an autosomal recessive juvenile-onset form of Parkinson's disease. As an E3 ubiquitin-ligase, parkin promotes the attachment of ubiquitin onto specific substrate proteins. Defects in the ubiquitination of parkin substrates are therefore believed to lead to neurodegeneration in Parkinson's disease.

A regulated interaction with the UIM protein Eps15 implicates parkin in EGF receptor trafficking and PI(3)K-Akt signalling.

Mutations in the parkin gene are responsible for a common familial form of Parkinson's disease. As parkin encodes an E3 ubiquitin ligase, defects in proteasome-mediated protein degradation are believed to have a central role in the pathogenesis of Parkinson's disease. Here, we report a novel role for parkin in a proteasome-independent ubiquitination pathway.

Clast4, the murine homologue of human eIF4E-Transporter, is highly expressed in developing oocytes and post-translationally modified at meiotic maturation.

In metazoans, translational regulation of a set of maternal mRNAs directs oocyte maturation and early embryogenesis. These transcripts are often kept dormant until their products are spatially and temporally required in development. The interaction between general translation factors (i.

Characterization of the host proinflammatory response to tumor cells during the initial stages of liver metastasis.

The influx of metastatic tumor cells into the liver triggers a rapid proinflammatory cytokine cascade. To further analyze this host response, we used intrasplenic/portal inoculation of green fluorescent protein-marked human and murine carcinoma cells and a combination of immunohistochemistry and confocal microscopy. The metastatic murine lung carcinoma H-59 or human colorectal carcinoma CX-1 cells triggered tumor necrosis factor (TNF)-alpha production by Kupffer cells located in sinusoidal vessels around the invading tumor cells.

Prognostic significance of p53, bcl-2, and Bax expression in early breast cancer.

Background: The use of adjuvant chemotherapy in early breast carcinoma is controversial, with most advocating its use in high-risk patients as defined by specific clinicopathologic parameters. Both bcl-2 and p53, which play a role in determining tumor growth by their effects on apoptosis and cell proliferation respectively, may serve to delineate this subset more accurately. The purpose of this study was to determine the prognostic value of bcl-2, Bax, and mutant p53 in stage I breast cancer.

Omega-6 fatty acids can inhibit Fas-mediated apoptosis in a human colorectal carcinoma cell line: a potential mechanism for escape from immune surveillance.

The Fas/Fas ligand pathway may play an important role in the pathogenesis of colorectal carcinoma by allowing tumor cells to evade host immune defenses. Since dietary fats, in particular omega-6 fatty acids, facilitate tumor development their influence on the Fas/Fas ligand pathway needs to be elucidated. The purpose of this study was to determine the effect of membrane free fatty acid (FFA) alterations on Fas expression and sensitivity.

Wnt signaling in the ovary: identification and compartmentalized expression of wnt-2, wnt-2b, and frizzled-4 mRNAs.

Ovarian cadherins, in addition to acting as structural (adhesion) molecules, also function as modulators of gene activity. The dual role of beta-catenin as an intracellular component of the cadherin adhesion complex and as a transcription factor provides a possible explanation for these cadherin effects. Because the transcriptional activity of beta-catenin is dependent on activation by the wnt signaling cascade, we examined whether components of this cascade are expressed in the rat ovary.

Bcl-2 is a useful prognostic marker in Dukes' B colon cancer.

Background: Currently, the use of adjuvant therapy specifically in Dukes' B colon cancers is controversial, emphasizing the importance of identifying prognostic markers to select patients for such therapy. Bcl-2 plays an important role in apoptosis regulation of solid tumors, such as colon and breast cancer, and is normally expressed in the base of the colonic crypts. The purpose of this study is to determine whether or not bcl-2 expression can be used to predict survival in Dukes' B colon cancer patients.

omega-3 fatty acids decrease endothelial adhesion of human colorectal carcinoma cells.

Background: Diets rich in omega-3 fatty acids have been shown to decrease both the initiation and promotion of colon carcinogenesis although their effect on hepatic metastasis formation is less well understood. Since adhesion of human colorectal carcinoma (HCRC) cells to hepatic endothelial cells is an important step in the metastatic cascade, the effect of membrane omega-3 fatty acid alterations on endothelial cell adhesion was studied.

Materials And Methods: CX-1 cells, a moderately differentiated HCRC cell line known to produce hepatic metastases in an athymic mouse intrasplenic injection model, were used.

Rapid induction of cytokine and E-selectin expression in the liver in response to metastatic tumor cells.

The cytokine-inducible endothelial cell adhesion receptor E-selectin has been implicated in cancer metastasis. Previously, we reported that experimental liver metastasis of Lewis lung carcinoma subline H-59 cells could be abrogated in animals treated with an anti-E-selectin antibody. To gain further insight into the functional relevance of E-selectin expression to liver colonization, we investigated here the time course of cytokine and hepatic E-selectin expression after the intrasplenic/portal inoculation of H-59 cells by using a combination of reverse transcription-PCR, Northern blot analysis, immunohistochemistry, and in situ hybridization.

Biologically active Fas antigen and its cognate ligand are expressed on plasma membrane-derived extracellular vesicles.

Exfoliation of plasma membrane components is a directed process that consumes energy and requires active cell metabolism. Proteins involved in regulating the survival and proliferation of eukaryotic cells are released on exfoliated vesicles. We examine here whether the Fas receptor and its cognate ligand (FasL) are present on vesicles shed from high metastatic potential CX-1 cells and low metastatic potential MIP-101 cells and from HuT 78 cells, respectively.

Apoptosis induced in human colorectal carcinoma by anti-Fas antibody.

Background: Apoptosis or programmed cell death has been shown to play an important role in the progression from polyps to carcinomas. Fas/APO-1 is a cell surface protein that can induce apoptosis in a variety of cell types upon specific binding. In this study seven human colorectal carcinoma (HCRC) cell lines of varying differentiation were analyzed for cell surface Fas expression.