title: LTE1 promotes exit from mitosis by multiple mechanisms.
abstract: In budding yeast, alignment of the anaphase spindle along the mother-bud axis is crucial for maintaining genome integrity. If the anaphase spindle becomes misaligned in the mother cell compartment, cells arrest in anaphase because the mitotic exit network (MEN), an essential Ras-like GTPase signaling cascade, is inhibited by the spindle position checkpoint (SPoC). Distinct localization patterns of MEN and SPoC components mediate MEN inhibition. Most components of the MEN localize to spindle pole bodies. If the spindle becomes mispositioned in the mother cell compartment, cells arrest in anaphase due to inhibition of the MEN by the mother cell-restricted SPoC kinase Kin4. Here we show that a bud-localized activating signal is necessary for full MEN activation. We identify Lte1 as this signal and show that Lte1 activates the MEN in at least two ways. It inhibits small amounts of Kin4 that are present in the bud via its central domain. An additional MEN-activating function of Lte1 is mediated by its N- and C-terminal GEF domains, which, we propose, directly activate the MEN GTPase Tem1. We conclude that control of the MEN by spindle position is exerted by both negative and positive regulatory elements that control the pathway's GTPase activity.
authors: David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors: Jill E
authors: JE
authors: Falk
authors: David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors: Ian W
authors: IW
authors: Campbell
authors: Department of Biology, Emmanuel College, Boston, MA 02115.
authors: Kelsey
authors: K
authors: Joyce
authors: Department of Biology, Emmanuel College, Boston, MA 02115.
authors: Jenna
authors: J
authors: Whalen
authors: Department of Biology, Emmanuel College, Boston, MA 02115.
authors: Anupama
authors: A
authors: Seshan
authors: David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139 angelika@mit.edu.
authors: Angelika
authors: A
authors: Amon
mesh_terms: D000705:Anaphase; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D008941:Spindle Apparatus; D064048:Spindle Pole Bodies / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D020662:Guanine Nucleotide Exchange Factors; C089357:LTE1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C089965:TEM1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D020559:Monomeric GTP-Binding Proteins