1,721,019 research outputs found

    Role of pRB2/p130 in cellular growth regulation

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    Cellular growth control in multicellular organisms has been shown to be essential to maintaining homeostasis. The retinoblastoma family of tumor suppressor proteins, pRB, p107 and pRB2/p130, encode proteins that act as transcriptional repressors of cell cycle-regulating and -promoting genes. The three proteins share similar and overlapping, yet distinctive, structural and functional features. Obvious differences are time and regulation of expression and the regulation of the functionality of pRb, p107 and pRB2/p130 by phosphorylation. PRB2/p130 is unique in that it is preferentially expressed and active in differentiated and silenced cells. This review discusses retinoblastoma family protein functions and the role of pRB2/p130 in cellular regulation

    Conference on Basic and Clinical Aspects of Cell Cycle Control

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    Scientists of numerous medical and life science disciplines met in Siena, Italy to discuss the latest proceedings in basic and clinical research. General models of interconnected linear and back-feeding cell-cycle control pathways provide a basis for applied molecular research. Cell-cycle determining factors essential for the control of cellular homeostasis either become markers to determine characteristics of a disease and/or become therapeutic targets. Apart from animal and tissue culture models, molecular theories finally have to stand proof in clinical application and evaluation. Therefore, the clinical feedback to the basic scientist's bench is essential for necessary adjustments of their models to improve future approaches to research challenges. A select group of speakers provided the audience with such an interdisciplinary dialogue at the first International Conference on Basic and Clinical Aspects of Cell-Cycle Control from May 29 to 31, 2000 in Siena, Italy. (C) 2000 Wiley-Liss, Inc

    The family of retinoblastoma proteins

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    Our understanding of how the retinoblastoma family members, pRB/p105, pRB2/p130, and pRBL1/p107, regulate cellular properties has progressed significantly. Mechanisms have been described regarding how these proteins utilize properties of additional factors, such as histone deacetylases, to negatively regulate transcription. More importantly, the retinoblastoma proteins have been integrated within multiple cellular pathways, and a complex view has emerged on how the individual members respond to various external and internal stimuli. pRB/p105 is best described in its biochemical properties as well as in the resulting cellular functions. Less is known about pRB2/p130 and pRBL1/p107, but an improved map of their individual as well as redundant functions has been drawn over the last years. In this review we describe general aspects of the properties and functions of the three retinoblastoma family members and their protein-binding partners in cellular growth control

    From cell cycle regulation to angiogenesis: a dialogue between the basic and clinical sciences

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    Basic research in biological and medical disciplines has revealed fundamental aspects of the differentiation of single cells as well as the development of multicellular organisms. The combination of knowledge of intracellular and intercellular pathways controlling development and homeostasis in higher organisms is the key to understanding certain diseases that are associated with abnormalities in these pathways and developing strategies for fighting them. Today's high scientific output in a rapidly growing number of scientific journals requires great effort to keep up with the latest developments outside one's specialization. The tenth international conference of the International Society of Differentiation (ISD) therefore was a great opportunity for scientists of diverse fields of biological and medical research to learn about the latest developments in even remotely related branches of research and opening new perspectives. The authors have tried to conserve this spirit in reviewing main aspects of research presented at the conference

    The RB family of cell cycle regulatory factors

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    The intense investigation of the retinoblastoma 'tumor suppressor family' members, pRb, pRb2/p130, and p107, has revealed impressive mechanisms evolved to safeguard development and homeostasis in higher eukaryotes. Members of the retinoblastoma family are involved in implementing and controlling three major aspects of cellular life: (1) proliferative growth, (2) differentiation, and (3) apoptosis. The activities of these proteins are highly regulated, enabling them to precisely establish control. The pRb protein is well understood in its regulatory abilities and is considered a classical tumor suppressor. The role of pRb2/p130 protein in growth suppression and its potential as a tumor suppressor have been established during the last few years. The p107 protein, structurally and functionally similar to, but yet distinctive from, pRb2/p130, is characterized at a more rudimentary level. In this report, we review the latest data on the retinoblastoma protein family and its web of regulatory mechanisms

    The COOH-terminal region of pRb2/p130 binds to histone deacetylase 1 (HDAC1), enhancing transcriptional repression of the E2F-dependent cyclin A promoter

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    The tumor suppressor retinoblastoma protein family members pRb, p107, and pRb2/p130 are potent negative transcriptional regulators. The best understood target is the transcription factor E2F, which activates cell cycle-dependent transcription of genes controlling and promoting the cell division cycle (e.g., cyclin A). pRb2/p130 is known to be important in implementing cell cycle exit into G0 due to serum deprivation or various differentiation programs. Several recent studies demonstrated the effect histone acetylases and histone deacetylases (HDACs) have on fine-tuning transcriptional regulation of eucaryotic cells. In this study, we demonstrate that pRb2/p130 binds to HDAC1. This interaction increases the ability of pRb2/p130 to inhibit transcription of the E2F-dependent cyclin A promoter in vivo. We also identify the COOH-terminal 35aa as being necessary for stable interaction between HDAC1 and pRb2/p130
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