Divisió cel·lular als vertebrats adults Constantment

1. ELS ORGANISMES PLURICEL·LULARS SÓN GENERATS PER MITJÀ DE SEQUÈNCIES COMPLEXES DE DIVISIONS CEL·LULARS • Divisió cel·lular als vertebrats adults • Constantment • Medul·la òssia (generació de les cèl·lules sanguínies • Epitelis (epidermis, intestí,...) • Algunes glàndules (Ex. sebàcies) • Gònades (gametogènesi) • Quan és necessari • Pell (dermis i epidermis després de lesions) • Fetge (després d’una pèrdua parcial) • Mai • Neurones Fins i tot a l’organisme adult és necessària la divisió cel·lular constant

2. FASES DEL CICLE CEL·LULAR Figure 13-1. The fate of a single parental chromosome throughout the eukaryotic cell cycle. Although chromosomes condense only during mitosis, they are shown in condensed form to emphasize the number of chromosomes at different cell-cycle stages. The nuclear envelope is not depicted. Following mitosis (M), daughter cells contain 2n chromosomes in diploid organisms and 1n chromosomes in haploid organisms including yeasts maintained in the haploid state. In proliferating cells, G1 is the period between “birth” of a cell following mitosis and the initiation of DNA synthesis, which marks the beginning of the S phase. At the end of the S phase, cells enter G2 containing twice the number of chromosomes as G1 cells (4n in diploid organisms). The end of G2 is marked by the onset of mitosis, during which numerous events leading to cell division occur. The G1, S, and G2 phases are collectively referred to as interphase, the period between one mitosis and the next. Most nonproliferating cells in vertebrates leave the cell cycle in G1, entering the G0 state.(Font: Lodish et al., 2000)

3. CONTROL DEL CICLE CEL·LULAR Figure 17-10. Two key components of the cell-cycle control system. A complex of cyclin with Cdk acts as a protein kinase to trigger downstream processes. Without cyclin, Cdk is inactive.(Font: Alberts et al., 1993) Figure 17-9. Checkpoints and inputs of regulatory information to the cell-cycle control system. Feedback from downstream processes and signals from the environment can prevent the control system from passing through certain specific checkpoints. The most prominent checkpoints are where the control system activates the triggers shown in yellow boxes. (Font: Alberts et al., 1993)

4. REGULACIÓ DEL CICLE CEL·LULAR Figure 13-2. Current model for regulation of the eukaryotic cell cycle. Passage through the cycle is controlled by G1, S-phase, and mitotic cyclin-dependent kinase complexes (CdkCs) highlighted in green. These are composed of a regulatory cyclin subunit and a catalytic cyclin-dependent kinase subunit. Protein complexes (orange) in the Cdc34 pathway and APC pathway polyubiquitinate specific substrates including the S-phase inhibitor, anaphase inhibitor, and mitotic cyclins, marking these substrates for degradation by proteasomes. These pathways thus drive the cycle in one direction because of the irreversibility of protein degradation. Proteolysis of anaphase inhibitors inactivates the protein complexes that connect sister chromatids at metaphase (not shown), thereby initiating anaphase.(Font: Lodish et al., 2000)

5. L’ESTUDI DEL CICLE CEL·LULAR ALS OVOCITS DE Xenopus VA PERMETRE DESCOBRIR EL FACTOR PROMOTOR DE LA MITOSI (MPF) Figure 17-15. Assaying for MPF by injection into a Xenopus oocyte. MPF can be detected because it drives the oocyte into M phase. The large nucleus (or "germinal vesicle") of the oocyte breaks down as the mitotic spindle forms. (Font: Alberts et al., 1993) L’ESTUDI DE DIFERENTS LLEVATS MUTANTS HA PERMÉS CARACTERITZAR MOLECULARMENT ELS PUNTS DE CONTROL DEL CICLE CEL·LULAR

6. ALS MAMÍFERS S’HAN TROBAT VARIES FORMES DE CICLINES I DE CDKs Figure 13-29. Activity of mammalian Cdkcyclin complexes through the course of the cell cycle in G0 cells induced to divide by treatment with growth factors. The width of the colored bands is approximately proportional to the protein kinase activity of the indicated complexes. Cyclin D refers to all three D-type cyclins. (Font: Lodish et al., 2000)

7. EL CICLE CEL·LULAR ÉS INDUÏT ALS MAMÍFERS PER FACTORS DE CREIXEMENT Figure 17-45. The response of Myc to a growth factor. Myc is the product of the early-response gene myc. The graph shows the changes in the concentration of Myc protein following a sudden increase in growth factor concentration to a new steady value, which causes the cell to exit G0 and to proliferate. The changes in Myc concentration reflect changes in myc gene transcription, stimulated by exposure of the cell to the growth factor. Myc protein itself inhibits myc transcription, and this negative feedback is thought to explain why the level of Myc declines from its initial peak to a lower steady value. (Font: Alberts et al., 1993) Els factors de creixement activen la transcripció de gens d’expressió immediata. Aquests gens són proto-oncogens, poden mutar convertint-se en oncogens.

8. ALGUNES CARACTERÍSTIQUES DE LA FASE M • Condensació de la cromatina en cromosomes – fosforilació de condensines per M-Cdk • Vesiculació de la membrana nuclear - fosforilació de la làmina nuclear per M-Cdk • Augment de la inestabilitat dels microtúbuls que permet la organització del fus mitòtic - Fosforilació de Proteïnes Associades a Microtúbuls • Els orgànuls amb membrana (RE, Golgi) també es trenquen en vesícules. Es deté el trànsit vesicular • Duplicació del centrosoma. Figure 18-4. Centriole replication. The centriole pair is associated with the centrosome matrix (green). At a certain point in G1 phase the two centrioles separate by a few micrometers. During S phase a daughter centriole begins to grow near the base of each old centriole and at a right angle to it. The elongation of the daughter centriole is usually completed by G2 phase. The two centriole pairs remain close together in a single centrosomal complex until the beginning of M phase, when the centrosome splits in two and the two halves begin to separate. (Font: Alberts et al., 1993)

9. FASES DE LA MITOSI (Font: Alberts et al., 1993)

10. (Font: Alberts et al., 1993)