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Molecular mechanisms underlying RB protein function

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TLDR
Several recent studies have found additional tumour-suppressor functions of RB, including alternative roles in the cell cycle, maintenance of genome stability and apoptosis, and are combining to define the multifunctionality of RB.
Abstract
Inactivation of the RB protein is one of the most fundamental events in cancer. Coming to a molecular understanding of its function in normal cells and how it impedes cancer development has been challenging. Historically, the ability of RB to regulate the cell cycle placed it in a central role in proliferative control, and research focused on RB regulation of the E2F family of transcription factors. Remarkably, several recent studies have found additional tumour-suppressor functions of RB, including alternative roles in the cell cycle, maintenance of genome stability and apoptosis. These advances and new structural studies are combining to define the multifunctionality of RB.

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Replication stress and cancer

TL;DR: The link between persistent replication stress and tumorigenesis is discussed, with the goal of shedding light on the mechanisms underlying the initiation of an oncogenic process, which should open up new possibilities for cancer diagnostics and treatment.
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Revisiting the hallmarks of cancer.

TL;DR: This work defines seven hallmarks of cancer: selective growth and proliferative advantage, altered stress response favoring overall survival, vascularization, invasion and metastasis, metabolic rewiring, an abetting microenvironment, and immune modulation, while highlighting some considerations for the future of the field.
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Non-canonical functions of cell cycle cyclins and cyclin-dependent kinases

TL;DR: The roles of cyclins and their catalytic partners, the cyclin-dependent kinases, as core components of the machinery that drives cell cycle progression are well established, but increasing evidence indicates that these proteins also carry out important functions in other cellular processes, such as transcription, DNA damage repair, control of cell death, differentiation, the immune response and metabolism.
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Short linear motifs: ubiquitous and functionally diverse protein interaction modules directing cell regulation.

TL;DR: Interaction Modules Directing Cell Regulation Kim Van Roey, Bora Uyar,† Robert J. Weatheritt,‡ Holger Dinkel,† Markus Seiler,† Aidan Budd,† Toby J. Gibson,† and Norman E. Davey*.
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RB1: a prototype tumor suppressor and an enigma.

TL;DR: This review summarizes some recent developments in pRB research and focuses on progress toward answers for the three fundamental questions that sit at the heart of the pRB literature: What does pRB do?
References
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Journal ArticleDOI

The hallmarks of cancer.

TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
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The retinoblastoma protein and cell cycle control

TL;DR: The main role of pRB is to act as a signal transducer connecting the cell cycle clock with the transcriptional machinery, allowing the clock to control the expression of banks of genes that mediate advance of the cell through a critical phase of its growth cycle.
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A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma

TL;DR: The isolation of a complementary DNA segment that detects a chromosomal segment having the properties of the gene at this locus is described, which is expressed in many tumour types, but no RNA transcript has been found in retinoblastomas and osteosarcomas.
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The regulation of E2F by pRB-family proteins

TL;DR: The rapid growth in the size of the E2F literature hides the fact that several fundamental questions have not been fully answered, and the second section of this review details five unresolved issues that have been highlighted by recent publications.
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Effects of an Rb mutation in the mouse

TL;DR: A mouse strain has been constructed in which one allele of Rb is disrupted, and heterozygous animals are not predisposed to retinoblastoma, but some display pituitary tumours arising from cells in which the wild-type Rb allele is absent.
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