Volume 11 Issue 9, September 2009

Centrosome duplication is under strict control such that it occurs only once per cell cycle. New insights into the molecular mechanisms that control centrosome number come from the discovery of a role for SADB kinase in centrosome biogenesis.

The RNA-induced silencing complex (RISC) downregulates expression of the genes targeted by RNA-silencing pathways. But formation and turnover of the RISC complex itself is tightly regulated and requires endosomal membranes.

Transcriptional cycling of activated glucocorticoid receptor (GR) and ultradian glucocorticoid secretion are well established processes. Ultradian hormone release is now shown to result in pulsatile gene transcription through dynamic exchange of GR with the target-gene promoter and GR cycling through the chaperone machinery.

Aurora A, an integral mitotic kinase, is essential for microtubule dynamics of post-mitotic neurons. PKCζ activates Aurora A, which in turn phosphorylates NDEL1 to promote neurite extension. This raises the possibility that Aurora A may also be involved in establishing cell polarity and axon/dendrite elaboration in young neurons.

Neurite extension requires regulation of microtubule dynamics. aPKC phosphorylates and activates Aurora A, leading to its accumulation at the neurite hillock where Aurora A phosphorylates NDEL1 to induce microtubule extension into neurites.

Radial centrosomal microtubules have a role in Golgi positioning. Golgi-derived microtubules organized by CLASP are now shown to be required for the unique ribbon-like morphology of the Golgi by bringing together individual Golgi stacks. Disrupting Golgi-derived microtubules leads to defects in polarized secretion and directional cell-migration.

The SADB kinase is shown to control centrosome duplication by localizing to centrosomes and phosphorylating the centrosomal component g-tubulin on Ser 131. Overexpression of SADB or of a phosphomimetic γ-tubulin mutant results in centrosome amplification.

Corticosteroid release in animals is highly pulsatile. Expression of glucocorticoid receptor-regulated genes is induced in a pulse-like manner and is coupled to hormone release in cultured cells and in vivo. Gene pulsing involves rapid receptor exchange on the promoter and cycling through the chaperone machinery.

Meiosis I differs from meiosis II and mitosis in that sister kinetochores need to be co-oriented to segregate to the same pole. Mis12, a conserved component of the kinetochore core, is required to link kinetochores together during reductional division.

Dam1 is a component of the microtubule-binding DASH complex. Artificial recruitment of Dam1 to yeast mini-chromosomes can compete with endogenous kinetochores for microtubule binding and rescue chromosome segregation in the absence of centromeres.

Ask1 is a component of the microtubule-binding DASH kinetochore complex. Targeting Ask1 to a yeast plasmid lacking centromeres promotes the recruitment of other kinetochore components and rescues bi-orientation and chromosome segregation.

Ubiquitin-mediated degradation influences embryonic axis formation by regulating the stability of ventrally expressed transcription factors, although it is unclear whether dorsal factors are similarly modulated. In Zebrafish, the E3 ubiquitin ligase Lnx-l acts on the dorsal transcriptional repressor Boz to control dorso-ventral axis formation.

The tumour suppressor p53 induces either apoptosis or cell-cycle arrest upon genotoxic stress. A regulatory network based on a complex of p53, the signalling protein axin, the p53 kinase HIPK2, the DNA repair-associated acetyltransferase Tip60 and Pirh2 governs the cellular response to p53 activation.

p53-mediated replicative cellular senescence is a barrier to tumorigenesis. The p53 isoforms p53β and Δ133p53 are respectively induced and downregulated during replicative senescence. Elevated p53β and reduced Δ133p53 levels are observed in colon adenomas with senescent phenotypes, whereas the opposite is found in colon carcinomas that might have escaped from the senescence barrier.

The ESCRT complex mediates sorting of ubiquitylated endosome-associated proteins into multivesicular bodies (MVBs). The RNA-induced silencing complex (RISC) components GW182 and AGO2 localize to membrane structures that congregate with MVBs. Loss of ESCRT function compromises miRNA-mediated silencing and increases GW182 levels, suggesting that ESCRT regulates RNAi by acting on GW182 turnover.

The Hermansky-Pudlak Syndrome 4 protein (HPS4) mediates trafficking between late endosomes and lysosomes and is now shown to inhibit small RNA-mediated silencing (RNAi) in flies and human cells. Components of the ESCRT complex, which mediates late endosome trafficking, are required for efficient miRNA-mediated silencing and additional results support the idea that RNAi effectors are functionally linked to endosome-associated compartments.

The RNA-binding protein Zcchc11 regulates cytokine expression in response to inflammation, although it was unclear how. Zcchc11 is shown to be an uridyltransferase that acts on mature cytokine-targeting miR-26b to influence interleukin-6 expression.