Forkhead transcription factors, Fkh1p and Fkh2p, collaborate with Mcm1p to control transcription required for M-phase

AGRADECIMIENTOS vi viiDurante toda esta tesis veía clarísimo todo lo que escribir en este apartado y ahora que llega el momento me quedo en blanco... Debe ser la presión de saber que va a ser la sección más leída… Primero agradecer a José y a Elena el poder haber trabajado en este laboratorio durante este tiempo. Han sido casi dos tesis, sí, sí, mi primera página del cuaderno de laboratorio data del 19 de Abril del 2000, todavía recuerdo el primer día, lo primero que hice fue rotular eppendorfs con una temblorosa mano, cuántos nervios. Después de trabajar en muchos temas, momentos difíciles y agradables, odiosos y entrañables, mudanzas, meetings, reuniones, cenas y mil otros recuerdos que me llevo puedo decir que me va a costar estar lejos de este lugar. Un abrazo muy fuerte a los dos!! Mis compañeros de laboratorio, pasados, presentes y futuros, desde aquel chico de la UAB que me enseñó como utilizar una enzima de restricción hasta el chico nuevo que todavía no conozco... No tengo palabras. Habéis sido mi familia todo este tiempo:A la pequeña Ester que me ha cuidado desde el principio como una hermana mayor. A Ana con la que el odio y el cariño se entrelazaban continuamente, muy buena conversadora y con gran ojo crítico. A Carine cuya breve estancia me dejó entrever que hay más de una manera de hacer ciencia. A Jordi (MalaP), compañero de adversidades y aventuras. A Mercè, cuyo apoyo logístico y moral ha sido imprescindible. A Alice, símbolo de la ternura y de la filología italiana, ya se sabe, a caballo donato... A Miriam, una de las mejores personas que conozco, sensata, seria y muy inteligente, una gran científica. A Mónica, maestra de artes marciales y colis. A Blanca, la dulzura personificada y buen público para los chistes. A Nati, también compañera de poyata, penas y alegrías, una post-doc todavía sin título. A Isabel, la catol... una gran amiga y compañera de ChIPs, tranquila que las cosas se van arreglando solas! A Sarela, un meiga pero de las buenas y a Iván (el granaíno), que con su corta pero intensa estancia nos alegró las largas horas de laboratorio. A todos gracias por apoyarme, aguantarme y porque nadie mejor que vosotros sabe lo que supone esta tesis.Al resto de gente de la UPF, los vecinos de laboratorio, especialmente el laboratorio de Señalización Celular (o cariñosamente llamados "los posas") con los que hemos compartido más que un laboratorio, Inmunología (Mari, Bea, Mingui, Julia, Rosa, etc.), grandes amigos dentro y fuera de la UPF, y todos los demás grupos del departamento.Siguiendo la ampliación de espacio, gracias también a toda la gente del PRBB que han ayudado a que estos años se hicieran más amenos. Gracias a ellos se materializó viii la mejor terapia antiestrés, el voley, gracias a los Rabenessen de Caramel (incluido Iván, sí, podrás venir al pica pica de mi tesis, jeje).Gracias a mis compañeros de licenciatura, con ellos inicié este camino y espero seguir sendas cercanas a las suyas.A la gente del laboratorio de Paul Nurse en New York, gracias por haberme hecho pasar una de las m...

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“…FKH1, FKH2 and HCM1 participate in the regulation of various cell cycle processes (Kumar et al, 2000), FKH1…”

Section: Forkhead Transcription Factorsmentioning

confidence: 99%

Promoter-driven splicing regulation in fission yeast

Moldón

Malapeira

Gabrielli

et al. 2008

Nature

135

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“…The major part of this coordination is achieved by the sequential activation of a small number of transcription regulators (reviewed in Mendenhall and Hodge, 1998): MBF (a complex of Mbp1p and Swi6p) and SBF (a complex of Swi4p and Swi6p) are responsible for activating G1 transcription (Koch et al, 1993); Fkh1p and a complex formed by the cooperative promoter binding of Mcm1p and Fkh2p and a later recruitment of Ndd1p are responsible for activating G2/M transcription (Koranda et al, 2000;Kumar et al, 2000;Pic et al, 2000;Hollenhorst et al, 2001); Swi5p and Ace2p, which are themselves expressed during G2/M, are the transcription factors responsible for activating the greater part of the next wave of M/G1 transcription (Dohrmann et al, 1992;Toyn et al, 1997); and Mcm1p, this time alone, is additionally responsible for activating transcription of several other M/G1 genes (McInerny et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress

Shapira

Segal

Botstein

2004

MBoC

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The effects of oxidative stress on yeast cell cycle depend on the stress-exerting agent. We studied the effects of two oxidative stress agents, hydrogen peroxide (HP) and the superoxide-generating agent menadione (MD). We found that two small coexpressed groups of genes regulated by the Mcm1-Fkh2-Ndd1 transcription regulatory complex are sufficient to account for the difference in the effects of HP and MD on the progress of the cell cycle, namely, G1 arrest with MD and an S phase delay followed by a G2/M arrest with HP. Support for this hypothesis is provided by fkh1fkh2 double mutants, which are affected by MD as we find HP affects wild-type cells. The apparent involvement of a forkhead protein in HP-induced cell cycle arrest, similar to that reported for Caenorhabditis elegans and human, describes a potentially novel stress response pathway in yeast. INTRODUCTIONReactive oxygen species (ROS) are by-products of aerobic metabolism, but are also attributes of the extracellular environment. They pose a threat to organisms by damaging a variety of cellular macromolecules, including DNA, membrane lipids, and proteins and are implicated with carcinogenesis, aging, and numerous degenerative diseases (Finkel and Holbrook, 2000;Neumann et al., 2003). The major ROS derived from oxygen are superoxide ions, hydrogen peroxide (HP), and hydroxy radicals, ordered here by increasing reactivity (reviewed in Shackelford et al., 2000).Oxidative stress in yeast has been studied by exposing cells to agents that are already reactive, typically HP, or drugs that cause the intracellular accumulation of reactive oxygen species (Godon et al., 1998;Dumond et al., 2000;Gasch et al., 2000). Menadione (MD) is such a drug, generating reactive superoxide ions, which can be further oxidized to give HP (Monks et al., 1992;Shackelford et al., 2000). It has been previously reported that exposure to HP or MD results in a cell cycle arrest (Flattery-O'Brien and Dawes, 1998;Leroy et al., 2001). However, the arrest points are not similar for the two agents. MD was reported to arrest cells at the G1 phase of the cell cycle, whereas HP was suggested to cause a G2 arrest by an alternate mechanism from that affected by MD (Flattery-O'Brien and Dawes, 1998); others reported that HP exposure causes a delay in the S phase (Leroy et al., 2001).Hundreds of genes are regulated so that they are expressed at specific times in the cell cycle and not at others (Cho et al., 1998;Spellman et al., 1998). The major part of this coordination is achieved by the sequential activation of a small number of transcription regulators (reviewed in Mendenhall and Hodge, 1998): MBF (a complex of Mbp1p and Swi6p) and SBF (a complex of Swi4p and Swi6p) are responsible for activating G1 transcription (Koch et al., 1993); Fkh1p and a complex formed by the cooperative promoter binding of Mcm1p and Fkh2p and a later recruitment of Ndd1p are responsible for activating G2/M transcription (Koranda et al., 2000;Kumar et al., 2000;Pic et al., 2000;Hollenhorst et al., 2001); Swi5p and Ace2p...

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“…1b). Ndd1 is the activator of the Mcm1-Fkh2 transcription factor complex [21][22][23][24] . The protein levels of Ndd1 oscillate periodically and it has been previously speculated 28 that it might be degraded by the APC/C.…”

Section: Resultsmentioning

confidence: 99%

“…We thus set up an unbiased screen designed to probe the entire yeast proteome. During the pilot stage of this screen, we identified Ndd1, an essential protein, which activates the Mcm1-Fkh2 G2-specific transcription factor [21][22][23][24] . We show here that Ndd1 is an APC/C Cdh1 substrate and that the APC/C Cdh1 is a major regulator of the cell cycle-specific oscillations of Ndd1.…”

mentioning

confidence: 99%

Degradation of Ndd1 by APC/CCdh1 generates a feed forward loop that times mitotic protein accumulation

et al. 2015

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Ndd1 activates the Mcm1-Fkh2 transcription factor to transcribe mitotic regulators. The anaphase-promoting complex/cyclosome activated by Cdh1 (APC/C Cdh1 ) mediates the degradation of proteins throughout G1. Here we show that the APC/C Cdh1 ubiquitinates Ndd1 and mediates its degradation, and that APC/C Cdh1 activity suppresses accumulation of Ndd1 targets. We confirm putative Ndd1 targets and identify novel ones, many of them APC/C Cdh1 substrates. The APC/C Cdh1 thus regulates these proteins in a dual manner-both pretranscriptionally and post-translationally, forming a multi-layered feedforward loop (FFL). We predict by mathematical modelling and verify experimentally that this FFL introduces a lag between APC/C Cdh1 inactivation at the end of G1 and accumulation of genes transcribed by Ndd1 in G2. This regulation generates two classes of APC/C Cdh1 substrates, early ones that accumulate in S and late ones that accumulate in G2. Our results show how the dual state APC/C Cdh1 activity is converted into multiple outputs by interactions between its substrates.

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Forkhead transcription factors, Fkh1p and Fkh2p, collaborate with Mcm1p to control transcription required for M-phase

Abstract: Forkhead transcription factors have redundant roles in the control of CLB2 cluster genes during the G2-M period of the cell cycle, in collaboration with Mcm1p.

Cited by 163 publications

References 34 publications

Promoter-driven splicing regulation in fission yeast

Promoter-driven splicing regulation in fission yeast

Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress

Degradation of Ndd1 by APC/CCdh1 generates a feed forward loop that times mitotic protein accumulation

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