The C-terminal regions of Haspin proteins have a conserved kinase domain

tary sensor, which may influence the mechanical and electrical heart function and may possibly be involved in the regulation of the energy metabolism. In conclusion, our data demonstrate a significant progress towards the characterization of the functional role of ORs in the human heart. We could show that activation of OR51E1 by MCFA induces negative inotropy in human explanted heart preparations and leads to negative chronotropy in stem cell-derived cardiomyocytes, which could be reversed by our identified OR51E1 antagonist. Based on our results, we hypothesize that OR51E1 may play a role in the metabolic regulation of cardiac function. The involvement of heart diseases in pathophysiological processes can only be speculated in the absence of data from animal models or patient studies. Schematic depiction of INCENP in humans and the most commonly used model organisms to study the function of the CPC. The CENbox is shown in orange. The green box is the -tubulin binding region . Note that Drosophila INCENP contains a potential N-terminal Cdk1 site but not a recognizable -tubulin binding region. The amino acids shown to be responsible for binding to HP1 are depicted in black. Gray and white motifs are potential HP1 binding sites. Note that although Sli15 has a potential HP1 binding site, budding yeast lacks an HP1 homolog. The domain responsible for central spindle localization of human INCENP is shown in purple. This domain has a predicted coiled-coil structure conserved from Xenopus to humans. Therefore, these coiled-coil domains are also depicted in purple. Drosophila INCENP has a short coiled-coil domain, the function of which has not been studied yet. Moreover, Sli15 contains a microtubule-binding domain that PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19792551 is not a coiled-coil . For Pic1, no data are available on microtubule binding. The brown region is the IN-box including the TSS motif, which binds and activates Aurora B and is itself phosphorylated by Aurora B CPC member as well as inhibition of Aurora B in either fungi, fly, worm, frog, or mammalian cells gives rise to very similar phenotypes. Disturbance of CPC function results in chromosome congression and segregation defects due to stabilization of incorrect kinetochoremicrotubule attachments, an impaired function of the mitotic checkpoint and improper spindle formation. Moreover, cytokinesis is also impaired and cells that exit mitosis without a functional CPC are tetraploid and order MLN1117 eventually die or senesce. The severity of these defects seems to depend on the level of knockdown or kinase inhibition; certain functions of the CPC are already disturbed when the complex is only partially inhibited, while others may require complete inhibition. Importantly, Aurora B heterozygous knockout mice have an increased cancer incidence underscoring the essential role of the CPC in maintaining chromosomal stability. Mammalian Aurora B is closely related to members of the AGC family of Serine/Threonine kinases, and the Aurora family also comprises Aurora A and Aurora C. These kinases share a common consensus phosphorylation motif and substrate specificity is mainly achieved by specific kinase distribution patterns within cells or between cells: Aurora A localizes to the mitotic spindle, centrosomes, and midbody, while Aurora B is present at chromosomal arms, inner centromeres, the central spindle, and the midbody. Aurora C behaves very similar to Aurora B with respect to localization and function, but is mainly expressed in germ Chromosoma