Characterization and expression analysis of two human septin genes, PNUTL1 and PNUTL2

Zieger, Barbara; Tran, H. M.; Hainmann, Ina; Wunderle, Daniela; Zgaga-Griesz, A.; Bläser, Susanne; Ware, Jerry

doi:10.1016/s0378-1119(00)00527-8

Cited by 39 publications

(50 citation statements)

References 23 publications

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“…Instead, ARTS contains a stretch of 27 residues at its Cterminus, which is not found in any other known protein (17,18). Sept4_i1 (H5/PNUTL2) is the other splice variant of Sept4 gene (26,42). Although Sept4_i1 shares 83% amino acid identity with ARTS, it does not contain the 27 mer Cterminal domain of ARTS (ARTS-CTD) and cannot induce apoptosis (28).…”

Section: The Unique C-terminal Domain Of Arts Is Sufficient To Bind Tmentioning

confidence: 99%

Peptides Mimicking the Unique ARTS-XIAP Binding Site Promote Apoptotic Cell Death in Cultured Cancer Cells

Edison

Reingewertz

Gottfried

et al. 2012

Clinical Cancer Research

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Purpose: XIAP [X-linked inhibitor of apoptosis (IAP) protein] is the best characterized mammalian caspase inhibitor. XIAP is frequently overexpressed in a variety of human tumors, and genetic inactivation of XIAP in mice protects against lymphoma. Therefore, XIAP is an attractive target for anticancer therapy. IAP antagonists based on a conserved IAP-binding motif (IBM), often referred to as "Smac-mimetics," are currently being evaluated for cancer therapy in the clinic. ARTS (Sept4_i2) is a mitochondrial proapoptotic protein which promotes apoptosis by directly binding and inhibiting XIAP via a mechanism that is distinct from all other known IAP antagonists. Here, we investigated the ability of peptides derived from ARTS to antagonize XIAP and promote apoptosis in cancer cell lines.Experimental Design: The ability of synthetic peptides, derived from the C-terminus of ARTS, to bind to XIAP, stimulate XIAP degradation, and induce apoptosis was examined. We compared the response of several cancer cell lines to different ARTS-derived peptides. Pull-down assays were used to examine binding to XIAP, and apoptosis was evaluated using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, caspase activation, and Western blot analyses of caspase substrates.Results: The C-terminus of ARTS contains a unique sequence, termed ARTS-IBM (AIBM), which is important for binding to XIAP and cell killing. AIBM peptides can bind to XIAP-BIR3, penetrate cancer cells, reduce XIAP levels, and promote apoptosis.Conclusions: Short synthetic peptides derived from the C-terminus of ARTS are sufficient for binding to XIAP and can induce apoptosis in cancer cells. These results provide proof-of-concept for the feasibility of developing ARTS-based anticancer therapeutics.

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Section: The Unique C-terminal Domain Of Arts Is Sufficient To Bind Tmentioning

confidence: 99%

Peptides Mimicking the Unique ARTS-XIAP Binding Site Promote Apoptotic Cell Death in Cultured Cancer Cells

Edison

Reingewertz

Gottfried

et al. 2012

Clinical Cancer Research

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“…The diversity in the N-and C-terminal regions flanking the core of the 12 known septin genes is compounded by the extensive alternate splicing events that allow many of these genes to encode multiple isoforms [89][90][91][92][93][94][95]. For example, SEPT9 has at least 18 distinct transcripts encoding 15 polypeptides with long forms (SEPT9 v1, v2 and v3), intermediate forms (SEPT9 v4), and short forms (SEPT9 v5) (see Supplementary information 6).…”

Section: Septin Domainsmentioning

confidence: 99%

The pathobiology of the septin gene family

Hall

Russell

2004

The Journal of Pathology

287

283

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Septins are an evolutionarily conserved group of GTP-binding and filament-forming proteins that belong to the large superclass of P-loop GTPases. While originally discovered in yeast as cell division cycle mutants with cytokinesis defects, they are now known to have diverse cellular roles which include polarity determination, cytoskeletal reorganization, membrane dynamics, vesicle trafficking, and exocytosis. Septin proteins form homo-and heterooligomeric polymers which can assemble into higher-order filaments. They are also known to interact with components of the cytoskeleton, ie actin and tubulin. The precise role of GTP binding is not clear but a current model suggests that it is associated with conformational changes which alter binding to other proteins. There are at least 12 human septin genes, and although information on expression patterns is limited, most undergo complex alternative splicing with some degree of tissue specificity. Nevertheless, an increasing body of data implicates the septin family in the pathogenesis of diverse disease states including neoplasia, neurodegenerative conditions, and infections. Here the known biochemical properties of mammalian septins are reviewed in the light of the data from yeast and other model organisms. The data implicating septins in human disease are considered and a model linking these data is proposed. It is posited that septins can act as regulatable scaffolds where the stoichiometry of septin associations, modifications, GTP status, and the interactions with other proteins allow the regulation of key cellular processes including polarity determination. Derangements of such septin scaffolds thus explain the role of septins in disease states.

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“…Of the mammalian septin proteins studied to date, each has a unique tissue distribution (Caltagarone et al, 1998;Yagi et al, 1998;Beites et al, 1999;Xie et al, 1999;Zieger et al, 2000), some being expressed primarily in the brain (CDCrel-1) and others being broadly expressed (Nedd5). To determine the tissue distribution of MSF, we probed a rat tissue Western and found that MSF-immunoreactive species were readily detectable in all tissues studied, except for skeletal muscle and intestine ( Figure 1C).…”

Section: Expression Profile Of Msf Proteinsmentioning

confidence: 99%

The Mammalian Septin MSF Localizes with Microtubules and Is Required for Completion of Cytokinesis

Surka

Tsang

Trimble

2002

MBoC

247

297

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Cytokinesis in animal cells involves the contraction of an actomyosin ring formed at the cleavage furrow. Nuclear division, or karyokinesis, must be precisely timed to occur before cytokinesis in order to prevent genetic anomalies that would result in either cell death or uncontrolled cell division. The septin family of GTPase proteins has been shown to be important for cytokinesis although little is known about their role during this process. Here we investigate the distribution and function of the mammalian septin MSF. We show that during interphase, MSF colocalizes with actin, microtubules, and another mammalian septin, Nedd5, and coprecipitates with six septin proteins. In addition, transfections of various MSF isoforms reveal that MSF-A specifically localizes with microtubules and that this localization is disrupted by nocodazole treatment. Furthermore, MSF isoforms localize primarily with tubulin at the central spindle during mitosis, whereas Nedd5 is mainly associated with actin. Microinjection of affinity-purified anti-MSF antibodies into synchronized cells, or depletion of MSF by small interfering RNAs, results in the accumulation of binucleated cells and in cells that have arrested during cytokinesis. These results reveal that MSF is required for the completion of cytokinesis and suggest a role that is distinct from that of Nedd5.

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Characterization and expression analysis of two human septin genes, PNUTL1 and PNUTL2

Cited by 39 publications

References 23 publications

Peptides Mimicking the Unique ARTS-XIAP Binding Site Promote Apoptotic Cell Death in Cultured Cancer Cells

Peptides Mimicking the Unique ARTS-XIAP Binding Site Promote Apoptotic Cell Death in Cultured Cancer Cells

The pathobiology of the septin gene family

The Mammalian Septin MSF Localizes with Microtubules and Is Required for Completion of Cytokinesis

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