Disease relevance of IQG1

• HIV-1 Vpr induces defects in mitosis, cytokinesis, nuclear structure, and centrosomes [1].
• Blocking Nedd5 expression in astrocytoma cells by antisense interferes with the process of cytokinesis during cell division [2].
• The cells with pmk1 deleted (delta pmk1) are viable but show various defective phenotypes, including cell wall weakness, abnormal cell shape, a cytokinesis defect, and altered sensitivities to cations, such as hypersensitivity to potassium and resistance to sodium [3].
• RESULTS: Neuroblast cytokinesis is normal in vitro, producing a larger neuroblast and a smaller ganglion mother cell [4].
• The male sterility results both from failure of germ cells to complete cytokinesis and from defects in spermatid elongation and maturation [5].

High impact information on IQG1

• (2006) describe a new pathway, NoCut, that links the completion of chromosome segregation to the onset of cytokinesis in budding yeast [6].
• The forkhead protein Sep1p regulates mitotic genes in the first cluster, including Ace2p, which activates transcription in the second cluster during the M-G1 transition and cytokinesis [7].
• We use an inducible Cre-loxP system to show that loss of Trrap blocks cell proliferation because of aberrant mitotic exit accompanied by cytokinesis failure and endoreduplication [8].
• Nearly 90% were sensitive to other agents, and most new genes could be assigned to the following functional groups: chromatin remodeling, chromosome segregation, nuclear pore formation, transcription, Golgi/vacuolar activities, ubiquitin-mediated protein degradation, cytokinesis, mitochondrial activity and cell wall maintenance [9].
• Coronin is a protein involved in cell locomotion and cytokinesis of Dictyostelium discoideum [10].

Biological context of IQG1

• Cyk1p is diffused throughout most of the cell cycle but localizes to a ring structure at the mother-bud junction after the initiation of anaphase [11].
• In contrast, a different point mutation, mlc1-11, displayed defects in cytokinesis and in interactions with Myo2p and Iqg1p [12].
• Iqg1p (Cyk1p) was previously implicated in cytokinesis (Epp and Chant, 1997; Lippincott and Li, 1998; Osman and Cerione, 1998), as well as in the establishment of polarity and protein trafficking (Osman and Cerione, 1998) [13].
• Furthermore, in the absence of Cyk1p/Iqg1p, myosin II fails to undergo the contraction-like size change at the end of mitosis [14].
• Immunofluorescence staining shows that Mlc1p is localized to sites of polarized cell growth as well as the bud neck before and independently of Cyk1p [15].

Anatomical context of IQG1

• Cytokinesis requires the polarization of the actin cytoskeleton, the secretion machinery, and the correct positioning of the division axis [13].
• Cytokinesis in animal cells is accomplished through constriction of an actomyosin ring [1] [2] [3], which must assemble at the correct time and place in order to ensure proper division of genetic material and organelles [15].
• In its absence, cytokinesis can still be completed by a process (possibly localized cell-wall synthesis leading to septum formation) that appears to require septin function and to be facilitated by F-actin [16].
• Little is known about the molecular machinery that directs secretory vesicles to the site of cell separation during cytokinesis [17].
• BACKGROUND: Myosins are motor proteins involved in processes like cell motility, vesicle transport, or cytokinesis [18].

Associations of IQG1 with chemical compounds

• By serendipity, we found that forchlorfenuron (FCF, N-(2-chloro-4-pyridyl)-N-phenylurea, 4PU300), a synthetic plant cytokinin, disturbed cytokinesis in Saccharomyces cerevisiae [19].
• Ipl1p is the budding yeast member of the Aurora family of protein kinases, critical regulators of genomic stability that are required for chromosome segregation, the spindle checkpoint, and cytokinesis [20].
• Fungal cell wall septation and cytokinesis are inhibited by bleomycins [21].
• Members of the casein kinase 1 family of serine/threonine kinases are highly conserved from yeast to mammals and seem to play an important role in vesicular trafficking, DNA repair, cell cycle progression and cytokinesis [22].
• Aurora-B is an important serine/threonine kinase required for chromosome segregation and cytokinesis [23].

Physical interactions of IQG1

• Our results suggest that the delayed M/G1 transition in cdc15 mutants is due to a septin-dependent checkpoint that couples initiation of the cell cycle to the completion of cytokinesis [24].
• Cla4 is involved in budding and cytokinesis and interacts with Cdc42, a GTPase required for polarized cell growth [25].
• As a consequence, Cdc15 binds to the daughter pole and triggers cytokinesis [26].
• The Vrp1 HOT domain promotes cytokinesis by binding to the Hof1 SH3 domain and counteracting its inhibitory effect [27].
• Yeast Nop15p is an RNA-binding protein required for pre-rRNA processing and cytokinesis [28].

Enzymatic interactions of IQG1

• Towards the end of the cell cycle, the localization of Bud10p refines to a tight double ring which splits at cytokinesis into two single rings, one in each progeny cell [29].
• In haploids, Bud5 forms double rings that encircle the mother-bud neck and split upon cytokinesis so that each progeny cell inherits Bud5 at the axial division remnant [30].

Co-localisations of IQG1

• Consistent with a role in cytokinesis, Iqg1 co-localizes with an actin ring encircling the mother-bud neck late in the cell cycle -a putative cytokinetic ring [31].

Regulatory relationships of IQG1

• An IQGAP-related protein controls actin-ring formation and cytokinesis in yeast [31].
• Mlc1p promotes septum closure during cytokinesis via the IQ motifs of the vesicle motor Myo2p [17].
• The Bub2-dependent mitotic pathway in yeast acts every cell cycle and regulates cytokinesis [32].
• Cytokinesis in eukaryotes involves the regulated assembly and contraction of a ring comprising filamentous (F)-actin and myosin II [33].
• Overexpression of Cyk2p also blocks cytokinesis, most likely due to a loss of the septins from the bud neck, indicating that Cyk2p may also play a role in regulating the localization of the septins [34].

Other interactions of IQG1

• Iqg1p, a yeast homologue of the mammalian IQGAPs, mediates cdc42p effects on the actin cytoskeleton [35].
• Iqg1p also appears to specify axial bud-site selection and mediates the proper localization of the septin, Cdc12p, as well as binds and helps localize the secretion landmark, Sec3p [13].
• The correlation between light chain structure and IQ sequence is demonstrated further by sedimentation velocity analysis of complexes of Mlc1p with IQ motifs from Myo2p and Iqg1p [36].
• We also show two-hybrid interactions between Iqg1p and Afr1p, a septin-binding protein involved in projection formation (Konopka, J.B., C. DeMattei, and C. Davis. 1995. Mol. Cell. Biol. 15:723-730) [35].
• Saccharomyces cerevisiae Mob1p is required for cytokinesis and mitotic exit [37].

Analytical, diagnostic and therapeutic context of IQG1

• Here, we demonstrate that, in addition to mitotic exit, S. cerevisiae MEN gene MOB1 is required for cytokinesis and cell separation [37].
• Using fluorescence time-lapse imaging and electron microscopy techniques, we show that cytokinesis in this strain is achieved through formation of multiple aberrant septa [38].
• Microinjection experiments and in vitro transfection assays have suggested a requirement for small GTPases of the Rho family in cytokinesis [39].
• Indirect immunofluorescence microscopic study demonstrated that Rho1p was concentrated to the periphery of the cells where cortical actin patches were clustered, including the site of bud emergence, the tip of the growing buds, and the mother-bud neck region of cells prior to cytokinesis [40].
• By carrying out time-lapse and optical sectioning video microscopy analysis of cells that express green fluorescent protein (GFP)-tagged nuclear envelope and actomyosin ring components, we found that nuclear division is temporally coupled to cytokinesis [41].

References