High impact information on TEM1

• In S. cerevisiae cells undergoing anaphase, a ras-related GTPase, Tem1, is located on the spindle pole body that enters the daughter cell and activates a signal transduction pathway, MEN, to allow mitotic exit [1].
• During mitosis, a ras-related GTPase (Tem1) binds GTP and activates a signal transduction pathway to allow mitotic exit [2].
• We also find that the presence of Tem1 and Lte1 in the bud is required for mitotic exit [3].
• We find that the GTP binding protein Tem1, a regulator of mitotic exit, is present on the spindle pole body that migrates into the bud during S phase and mitosis [3].
• Thus, Tem1 and Lte1 are present in the same cellular compartment (the bud) only after the nucleus enters the bud during nuclear division [3].

Biological context of TEM1

• The yeast TEM1 gene, which encodes a GTP-binding protein, is involved in termination of M phase [4].
• We have identified TEM1 as a gene that, when present on a multicopy plasmid, suppresses the cold-sensitive phenotype of lte1 [4].
• The defect of TEM1 was lethal, and the tem1-defective cells were arrested at telophase with high H1-kinase activity under restrictive conditions, indicating that TEM1 is required to exit from M phase [4].
• Unlike TEM1, LTE1 is not restricted to mitosis but is expressed throughout the cell cycle [5].
• These data support the view that the spindle assembly checkpoint encompasses regulation of distinct mitotic steps, including a MAD2-directed block to anaphase initiation and a BUB2-directed block to TEM1-dependent exit [6].

Associations of TEM1 with chemical compounds

• Inappropriate sister chromatid separation in nocodazole-treated bub2 cells is prevented when mitotic exit is blocked using a conditional tem1(c) mutant, indicating that the preanaphase failure in bub2 cells is a consequence of events downstream of TEM1 in the mitotic exit pathway [6].
• By random mutagenesis of Bfa1-D8(391-574) with hydroxylamine, we isolated a point mutant of D8, D8(E438K), which interacts with both Tem1p and Bub2p but cannot respond to checkpoint signals [7].

Physical interactions of TEM1

• These findings suggested the hypothesis that movement of the spindle pole through the neck allows Tem1p to interact with Lte1p, promoting GTP loading of Tem1p and mitotic exit [8].
• Thus, in nud1-2 cells the failure of Tem1p to interact with Cdc15p at the SPB probably prevents mitotic exit [9].

Regulatory relationships of TEM1

• The defect of TEM1 was suppressed by a high dose of CDC15, which encodes a protein kinase homologous to mitogen-activated protein kinase kinase kinases [4].
• Bfa1 can regulate Tem1 function independently of Bub2 in the mitotic exit network of Saccharomyces cerevisiae [10].
• In budding yeast, activation of the small Ras-like GTPase Tem1 triggers exit from mitosis and cytokinesis [11].
• The Tem1 small GTPase controls actomyosin and septin dynamics during cytokinesis [12].

Other interactions of TEM1

• Both events depend on the mitotic exit pathway components TEM1 and CDC15 [13].
• In the spindle checkpoint pathway, this is accomplished through Bfa1/Bub2, a heteromeric GTPase-activating protein (GAP) that inhibits Clb degradation by keeping the G protein Tem1 inactive [3-5] [14].
• Tem1 is required for Cdc14 activation [14].
• By sequence analysis, Tem1p has highest similarity to Vps21p (yeast homolog of mammalian Rab5) [5].
• In addition, inhibition of PAK kinases by Cla4t prevents mitotic exit also by a Swe1-independent mechanism impinging directly on the MEN activator Tem1 [15].

Analytical, diagnostic and therapeutic context of TEM1

• Sequence analysis of TEM1 and GTP-binding analysis of the gene product revealed that TEM1 encodes a novel low-molecular-weight GTP-binding protein [4].

References