Bid en ciclo celular

Dos nuevos reportes en Cell hablan de que Bid se localiza en nucleo, en donde media parte de la respuesta al daño al ADN, via ATM. Bid pareceria ser muy importante en el checkpoint de la fase S.
A Role for Proapoptotic BID in the DNA-Damage Response
Sandra S. Zinkel,^1,3,4,* Kristen E. Hurov,^1,3 Christy Ong,¹ Farvardean M. Abtahi,¹ Atan Gross,² and Stanley J. Korsmeyer¹
Proapoptotic BID Is an ATM Effector in the DNA-Damage Response
Iris Kamer,^1,4 Rachel Sarig,^1,4 Yehudit Zaltsman,¹ Hagit Niv,¹ Galia Oberkovitz,¹ Limor Regev,¹ Gal Haimovich,¹ Yaniv Lerenthal,² Richard C. Marcellus,³ and Atan Gross^1,*
Cell, Vol 122, 593-603, 26 August 2005

The p53 pathway: positive and negative feedback loops

The p53 pathway responds to stresses that can disrupt the
fidelity of DNA replication and cell division. A stress
signal is transmitted to the p53 protein by post-translational
modifications. This results in the activation of the
p53 protein as a transcription factor that initiates a
program of cell cycle arrest, cellular senescence or
apoptosis. The transcriptional network of p53-responsive
genes produces proteins that interact with a large number
of other signal transduction pathways in the cell and a
number of positive and negative autoregulatory feedback
loops act upon the p53 response. There are at least seven
negative and three positive feedback loops described here,
and of these, six act through the MDM-2 protein to
regulate p53 activity. The p53 circuit communicates with
the Wnt-beta-catenin, IGF-1-AKT, Rb-E2F, p38 MAP
kinase, cyclin-cdk, p14/19 ARF pathways and the cyclin
G-PP2A, and p73 gene products. There are at least three
different ubiquitin ligases that can regulate p53 in an
autoregulatory manner: MDM-2, Cop-1 and Pirh-2. The
meaning of this redundancy and the relative activity of
each of these feedback loops in different cell types or
stages of development remains to be elucidated. The
interconnections between signal transduction pathways
will play a central role in our understanding of cancer.

Oncogene (2005) 24, 2899–2908

Gran batalla en EU contra la teoría de la evolución de Darwin.

En el New York Times se publicó este artículo.
...Algo llamado "diseño inteligente" es la "teoría" avanzada como contrapropuesta a la teoría de Darwin, y después de una década de inversiones multimillonarias para financiar y promover académicos, publicaciones y esfuerzos de propaganda, las fuerzas antidarwinistas han logrado su objetivo: colocar su "teoría" al centro del debate nacional y punta de lanza de las llamadas "guerras culturales" de este país entre las fuerzas conservadoras fundamentalistas cristianas y todos los "otros", incluyendo casi a toda la comunidad científica establecida...
Les dejo el link.
Magali.

http://www.jornada.unam.mx/2005/ago05/050823/030n1mun.php

Discovery of the ubiquitin proteasome system and its involvement in apoptosis

Hola a todos. En Cell Death and Differentiation, aparecen entrevistas de tres ganadores del premio nobel de química en el 2004. Las entrevistas y los artículos de revisión tratan del sistema de degradación (proteosoma) y ubiquitinación y su papel en la apoptosis. Les envío el link de la revista y el link de un artículo en dónde se habla de las IAPs y la ubiquitinación de proteínas.
Magali.

Revista
http://info.nature.com/cgi-bin24/DM/y/eUWy0JyZ8X0DK0GNW0Eq

IAPs - the ubiquitin connection, D L Vaux and J Silke

http://info.nature.com/cgi-bin24/DM/y/eUWy0JyZ8X0DK0kRy0E5

Malas noticias.

Este articulo aparecera proximamente en oncogene.

Inhibition of clonogenic tumor growth: a novel function of Smac contributing to its antitumor activity

Meike Vogler, Stavros Giagkousiklidis, Felicitas Genze, Juergen E Gschwend, Klaus-Michael Debatin and Simone Fulda

link

Oncogene advance online publication, August 8, 2005; doi:10.1038/sj.onc.1208876
While second mitochondria derived activator of caspase (Smac) has been described to sensitize for apoptosis, its effect on cell viability in the absence of apoptotic stimuli has remained unclear. Here, we report that Smac inhibits clonogenic tumor growth by blocking random migration and proliferation and by enhancing apoptosis in a cell density and cell type dependent manner in SH-EP neuroblastoma cells. Inhibition of clonogenic survival by overexpression of full-length or processed Smac strictly depended on low cell density, and was reversible by replatement at high density. We discovered that Smac inhibits cell motility and random migration at low cell density. In addition, Smac enhanced apoptosis and inhibited protein, but not mRNA expression of XIAP, survivin and other short-lived proteins (FLIP, p21), indicating that Smac may globally inhibit protein expression. Also, Smac inhibited proliferation and increased polynucleation with no evidence for polyploidy, cell cycle arrest or senescence indicating that Smac impaired cell division. Interestingly, inhibition of clonogenic capacity by Smac occurred independent of its apoptosis promoting activity. By demonstrating that Smac restrains clonogenic tumor growth, our findings may have important implications for control of tumor growth and/or its metastatic spread. Thus, Smac agonists may be useful in cancer therapy, for example, for tumor control in minimal residual disease.

Ingrid tenia resultados compatibles con esto. Sin embargo, ellos fueron mas rapidos.

Importante para todos

Este nuevo articulo recien publicado en cancer research nos dice que los complejos de NFkB activados por doxorrubicina, un antineoplasico, pueden ser inhibidores en vez de activadores. Esto es muy importante en nuestro contexto para los varios proyectos que tenemos y puede ser una nueva posibilidad de los diversos resultados que tenemos o tendremos. La copia de este y del otro de los articulos de cancer research los pondre en la compu del labo despues.


Nuclear factor-kappaB induced by doxorubicin is deficient in phosphorylation and acetylation and represses nuclear factor-kappaB-dependent transcription in cancer cells.
Cancer Res. 2005 May 15;65(10):4273-81.

The primary goal of chemotherapy is to cause cancer cell death. However, a side effect of many commonly used chemotherapeutic drugs is the activation of nuclear factor-kappaB (NF-kappaB), a potent inducer of antiapoptotic genes, which may blunt the therapeutic efficacy of these compounds. We have assessed the effect of doxorubicin, an anthracycline in widespread clinical use, on NF-kappaB activation and expression of antiapoptotic genes in breast cancer cells. We show that doxorubicin treatment activates NF-kappaB signaling and produces NF-kappaB complexes that are competent for NF-kappaB binding in vitro. Surprisingly, these NF-kappaB complexes suppress, rather than activate, constitutive- and cytokine-induced NF-kappaB-dependent transcription. We show that doxorubicin treatment produces RelA, which is deficient in phosphorylation and acetylation and which blocks NF-kappaB signaling in a histone deacetylase-independent manner, and we show that NF-kappaB activated by doxorubicin does not remain stably bound to kappaB elements in vivo. Together these data show that NF-kappaB signaling induced by doxorubicin reduces expression of NF-kappaB-dependent genes in cancer cells.

Articulos para el proximo lunes

Revisaremos un poco de la relacion de la mitosis, sus checkpoints, senesencia y el cancer. Para empezar tenemos una revision, para entender mejor los articulos.
Beth A.A. Weaver and Don W. Cleveland
Decoding the links between mitosis, cancer, and chemotherapy: The mitotic checkpoint, adaptation, and cell death
Cancer Cell 2005 8: 7-12

los articulos a revisar

Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype. Young-Woo Eom, Mi Ae Kim, Seok Soon Park, Mi Jin Goo, Hyuk Jae Kwon, Seonghyang Sohn, Wook-Hwan Kim, Gyesoon Yoon and Kyeong Sook Choi Oncogene 24: 4765-4777;

Cdc2 and Cdk2 play critical roles in low dose doxorubicin-induced cell death through mitotic catastrophe but not in high dose doxorubicin-induced apoptosis.
Biochem Biophys Res Commun. 2005 Sep 9;334(4):1014-21.

bcl-3 es reparador

Vilma nos envia este link
Bcl3 reparador
en donde reportan el articulo de science sobre el papel de reparador de DNA por Bcl-3. Algo interesante seria checar las vias y las proteinas que interaccionan in silico para probarlas in vivo.

Un link para revisar

Algunas son buenas.
PhDComics

Para los NFKBologos

El papel de la ubiquitacion y proteolisis en NFkB
Nature Cell Biology 7, 758 - 765 (2005)
Ubiquitin signalling in the NF-B pathway
The transcription factor NF-B controls many processes, including immunity, inflammation and apoptosis. Ubiquitination regulates at least three steps in the NF-B pathway: degradation of IB (inhibitor of NF-B), processing of NF-B precursors, and activation of the IB kinase (IKK). Recent studies have revealed several enzymes involved in the ubiquitination and deubiquitination of signalling proteins that mediate IKK activation through a degradation-independent mechanism.

Ah! y felicidades a Juan Carlos por ser el primero en colocar un comentario.

Link Directo al articulo completo

Cambios

Hola
Cambie el formato, agregue unas fotos y puse los links a los articulos completos.
Saludos
J.