https://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/159777/1/j.cell.2006.07.024.pdf

Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

TGFβ in Cancer

The basic elements of the transforming growth factor-β (TGFβ) pathway were revealed more than a decade ago. Since then, the concept of how the TGFβ signal travels from the membrane to the nucleus has been enriched with additional findings, and its multifunctional nature and medical relevance have relentlessly come to light. However, an old mystery has endured: how does the context determine the cellular response to TGFβ? Solving this question is key to understanding TGFβ biology and its many malfunctions. Recent progress is pointing at answers.

/pdf/tgfb-signalling-in-context-56apiue88r.pdf

TGFβ signalling in context.

Smad transcription factors lie at the core of one of the most versatile cytokine signaling pathways in metazoan biology-the transforming growth factor-beta (TGFbeta) pathway. Recent progress has shed light into the processes of Smad activation and deactivation, nucleocytoplasmic dynamics, and assembly of transcriptional complexes. A rich repertoire of regulatory devices exerts control over each step of the Smad pathway. This knowledge is enabling work on more complex questions about the organization, integration, and modulation of Smad-dependent transcriptional programs. We are beginning to uncover self-enabled gene response cascades, graded Smad response mechanisms, and Smad-dependent synexpression groups. Our growing understanding of TGFbeta signaling through the Smad pathway provides general principles for how animal cells translate complex inputs into concrete behavior.

/pdf/smad-transcription-factors-33kx764y26.pdf

Smad transcription factors

Malignant astrocytic gliomas such as glioblastoma are the most common and lethal intracranial tumors. These cancers exhibit a relentless malignant progression characterized by widespread invasion throughout the brain, resistance to traditional and newer targeted therapeutic approaches, destruction of normal brain tissue, and certain death. The recent confluence of advances in stem cell biology, cell signaling, genome and computational science and genetic model systems have revolutionized our understanding of the mechanisms underlying the genetics, biology and clinical behavior of glioblastoma. This progress is fueling new opportunities for understanding the fundamental basis for development of this devastating disease and also novel therapies that, for the first time, portend meaningful clinical responses.

/pdf/malignant-astrocytic-glioma-genetics-biology-and-paths-to-689wwbep62.pdf

Malignant astrocytic glioma: genetics, biology, and paths to treatment.

Activation of the tumour suppressor p53 by DNA damage induces either cell cycle arrest or apoptotic cell death1. The cytostatic effect of p53 is mediated by transcriptional activation of the cyclin-dependent kinase (CDK) inhibitor p21Cip1, whereas the apoptotic effect is mediated by transcriptional activation of mediators including PUMA and PIG3 (ref. 2). What determines the choice between cytostasis and apoptosis is not clear3. Here we show that the transcription factor Myc is a principal determinant of this choice. Myc is directly recruited to the p21Cip1 promoter by the DNA-binding protein Miz-1. This interaction blocks p21Cip1 induction by p53 and other activators. As a result Myc switches, from cytostatic to apoptotic, the p53-dependent response of colon cancer cells to DNA damage. Myc does not modify the ability of p53 to bind to the p21Cip1 or PUMA promoters, but selectively inhibits bound p53 from activating p21Cip1 transcription. By inhibiting p21Cip1 expression Myc favours the initiation of apoptosis, thereby influencing the outcome of a p53 response in favour of cell death.

Myc suppression of the p21 Cip1 Cdk inhibitor influences the outcome of the p53 response to DNA damage

http://europepmc.org/articles/PMC2692279?pdf=render

Hong-Van Le

Papers

Myc suppression of the p21 Cip1 Cdk inhibitor influences the outcome of the p53 response to DNA damage

Genome-wide Impact of the BRG1 SWI/SNF Chromatin Remodeler on the Transforming Growth Factor β Transcriptional Program

Cyclin-dependent Kinase Inhibitors Uncouple Cell Cycle Progression from Mitochondrial Apoptotic Functions in DNA-damaged Cancer Cells