New insights into the function of IAP proteins: modulation of the MYC/MAX/MAD network

A growing number of studies have revealed that the inhibitor of apoptosis (IAP) proteins play a variety of cellular roles in addition to suppression of apoptosis. A recent study in Molecular Cell demonstrates that one IAP member, c-IAP1, functions to potentiate the activity of Myc by triggering the ubiquitination and proteasomal degradation of the Myc inhibitory protein Mad1.     

Acute ablation of survivin uncovers p53-dependent mitotic checkpoint functions and control of mitochondrial apoptosis

Survivin is a member of the Inhibitor of Apoptosis gene family that has been implicated in cell division and suppression of apoptosis. Here, we show that preferential ablation of the nuclear pool of survivin by RNA interference produces a mitotic arrest followed by re-entry into the cell cycle and polyploidy. Survivin ablation causes multiple centrosomal defects, aberrant multipolar spindle formation, and chromatin missegregation, and these phenotypes are exacerbated by loss of the cell cycle regulator, p21(Waf1/Cip1) in p21(-/-) cells. The mitotic checkpoint activated by loss of survivin is mediated by induction of p53 and associated with increased expression of its downstream target, p21(Waf1/Cip1). Accordingly, p53(-/-) cells exhibit reduced mitotic arrest and enhanced polyploidy upon survivin ablation as compared with their p53(+/+) counterparts. Partial reduction of the cytosolic pool of survivin by RNA interference sensitizes cells to ultraviolet B-mediated apoptosis and results in enhanced caspase-9 proteolytic cleavage, whereas complete ablation of cytosolic survivin causes loss of mitochondrial membrane potential and spontaneous apoptosis. These data demonstrate that survivin has separable checkpoint functions at multiple phases of mitosis and in the control of mitochondrial-dependent apoptosis.     

Patterns of cervical metastasis from carcinoma of the oral tongue

Background  

Cancer of the oral tongue is the second most common cancer among males in various parts of India. Despite advances in diagnosis and treatment the failure rates in cancer of the oral tongue are high and survival poor. Majority of these failures occur in untreated neck.     

Constitutive proteasome-mediated turnover of Bfl-1/A1 and its processing in response to TNF receptor activation in FL5.12 pro-B cells convert it into a prodeath factor

Bfl-1/A1 is generally recognized as a Bcl-2-related inhibitor of apoptosis. We show that Bfl-1 undergoes constitutive ubiquitin/proteasome-mediated turnover. Moreover, while Bfl-1 suppresses apoptosis induced by staurosporine or cytokine withdrawal, it is proapoptotic in response to tumor necrosis factor (TNF) receptor activation in FL5.12 pro-B cells. Its anti- versus proapoptotic effect is regulated by two proteolytic events: (1) its constitutive proteasome-mediated turnover and (2) its TNF/cycloheximide (CHX)-induced cleavage by mu-calpain, or a calpain-like activity, coincident with acquisition of a proapoptotic phenotype. In vitro studies suggest that calpain-mediated cleavage of Bfl-1 occurs between its Bcl-2 homology (BH)4 and BH3 domains. This would be consistent with the generation of a proapoptotic Bax-like BH1-3 molecule. Overall, our studies uncovered two new regulatory mechanisms that play a decisive role in determining Bfl-1's prosurvival versus prodeath activities. These findings might provide important clues to counteract chemoresistance in tumor cells that highly express Bfl-1.     

The trimorphic flea-beetle, <Emphasis Type="Italic">Alagoasa extrema</Emphasis>, not suitable for biocontrol of <Emphasis Type="Italic">Lantana camara</Emphasis> in Africa

The biology and host range of the flea-beetle, Alagoasa extrema (Harold) (Coleoptera: Chrysomelidae: Galerucinae: Alticini), was studied under quarantine laboratory conditions to evaluate the insect’s suitability for release as a biological control agent for the noxious weed, Lantana camara L. (Verbenaceae), in South Africa. Identification of this species proved noteworthy. The adults of A. extrema display three freely interbreeding and very distinct colour morphs, which can be confused with no less than 11 species of Alagoasa found in Mexico and the southwestern U.S. Initially, specimens were identified as two species of the genus Alagoasa Bechyné, i.e. A. quadrilineata (Harold) and A. extrema. Thirteen additional Alagoasa species and Kushelina petaurista (F). that can be confused with A. extremabased on external morphology of adults or larvae are discussed. Favourable biological characteristics included long-lived adults, several overlapping generations per year, and high adult and larval feeding rates. Observations from the insect’s native Mexican range and studies in South Africa suggest that A. extrema would probably be more suited to subtropical, rather than temperate areas in Africa. Host-specificity studies showed A. extrema to be an oligophagous species, capable of feeding and developing on several non-target species, especially two indigenous, African Lippia species (Verbenaceae). The host suitability of these indigenous species was only marginally lower than that of L. camara, and the potential risk to them was deemed to be too high to warrant release. It was therefore recommended that A. extrema be rejected as biocontrol agent for lantana in Africa.     

A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif

Here we describe a protein product of the human septin H5/PNUTL2/CDCrel2b gene, which we call ARTS (for apoptosis-related protein in the TGF-beta signalling pathway). ARTS is expressed in many cells and acts to enhance cell death induced by TGF-beta or, to a lesser extent, by other apoptotic agents. Unlike related septin gene products, ARTS is localized to mitochondria and translocates to the nucleus when apoptosis occurs. Mutation of the P-loop of ARTS abrogates its competence to activate caspase 3 and to induce apoptosis. Taken together, these observations expand the functional attributes of septins previously described as having roles in cytokinesis and cellular morphogenesis.     

Intercontinental distribution of Plagiochila corrugata (Plagiochilaceae, Hepaticae) inferred from nrDNA ITS sequences and morphology

Plagiochila sect. Vagae is a large pantropical clade that is characterized morphologically by frequent terminal branching, vegetative distribution by propagules on the ventral surface of the leaves and a capsule wall with thickenings in all layers. Plagiochila corrugata from Brazil is characterized by strongly undulate, toothed leaf margins and represents the only known neotropical species of sect. Vagae with unispiral elaters. Plagiochila cambuena from Madagascar is distinguished by the same features. Maximum likelihood and parsimony analyses of 38 nrDNA ITS sequences of Plagiochila reveal P. corrugata and P. cambuena in a weakly (ML) to well (MP) supported monophyletic lineage within P.  sect.  Vagae . As an outcome of the morphological and molecular investigation, P. cambuena is relegated to the synonymy of P. corrugata. Plagiochila corrugata is placed in a Vagae -subclade with 11 further American species. The range of P. corrugata can be ascribed to long-range dispersal from the Neotropics rather than a Gondwanan distribution. Species from tropical Asia and Africa are placed at the base of the Vagae clade. Branch length within P.  sect.  Vagae points to a sudden radiation.  © 2004 The Linnean Society of London, Botanical Journal of the Linnean Society , 2004, 146 , 469–481.