AIM-1: a mammalian midbody-associated protein required for cytokinesis

Abstract

Mitosis is a highly coordinated process that assures the fidelity of chromosome segregation. Errors in this process result in aneuploidy which can lead to cell death or oncogenesis. In this paper we describe a putative mammalian protein kinase, AIM-1 (Aurora and Ipl1-like midbody-associated protein), related to Drosophila Aurora and Saccharomyces cerevisiae Ipl1, both of which are required for chromosome segregation. AIM-1 message and protein accumulate at G 2 /M phase. The protein localizes at the equator of central spindles during late anaphase and at the midbody during telophase and cytokinesis. Overexpression of kinase-inactive AIM-1 disrupts cleavage furrow formation without affecting nuclear division. Furthermore, cytokinesis frequently fails, resulting in cell polyploidy and subsequent cell death. These results strongly suggest that AIM-1 is required for proper progression of cytokinesis in mammalian cells.

Phosphorylation of p53 Is Regulated by TPX2-Aurora A in Xenopus Oocytes

“…Overexpression of either human or Xenopus Aurora A can transform mammalian cells, but only if p53 function is deficient. In tumors in which Aurora A is overexpressed, centrosome amplification is common and is thought to contribute to chromosomal instability (2,3,6,57). On the other hand, studies of mouse embryo fibroblasts from mice lacking p53 show that even after early passages, centrosome amplification occurs (26,27).…”

Subcellular localization and nucleocytoplasmic transport of the chromosomal passenger proteins before nuclear envelope breakdown

“…Aurora B is a member of a conserved family of serine/threonine protein kinases originally identified as a mammalian homologue of Drosophila and yeast proteins required for chromosome segregation (Bischoff et al, 1998;Terada et al, 1998). Aurora B phosphorylates a variety of substrate proteins and regulates many aspects of cell division, from chromosome condensation to cytokinesis (reviewed by Andrews et al, 2003).…”

p21Waf1/Cip1/Sdi1-induced growth arrest is associated with depletion of mitosis-control proteins and leads to abnormal mitosis and endoreduplication in recovering cells

“…Figure 4a shows the results of RT ± PCR assays demonstrating that IPTG treatment drastically decreases the RNA levels of a group of genes that control di erent stages of mitosis. These include CDC2 and cyclin B1 that form the mitosis-initiating complex (Kishimoto and Okumura, 1997), polo-like kinase (PLK1) that plays a role in the onset of mitosis, mitotic checkpoint control and cytokinesis (Glover et al, 1998), CDC2-interacting protein CKsHs1, a target of mitotic checkpoint control (Hixon et al, 1998), mitotic centromere-associated kinesin (MCAK; Kuriyama et al, 1995), a centrosome-associated kinase AIK1 involved in spindle formation (Kimura et al, 1997), centromere proteins CENP-A and CENP-F (Liao et al, 1995;Kalitsis et al, 1998), as well as MAD2 and BUBR1 genes that play a central role in the spindle checkpoint control (Li and Benezra, 1996;Chan et al, 1999), CHL1 helicase (a homolog of a yeast protein that plays a role in proper chromosome distribution during mitosis; Gerring et al, 1990), and genes for three proteins involved in cytokinesis, Prc1, Aim1 and citron kinase (Jiang et al, 1998;Terada et al, 1998;Madaule et al, 1998). IPTG-induced decay of the corresponding proteins has also been con®rmed for several of these genes by immunoblotting (Figure 4b).…”