p21 in cancer: intricate networks and multiple activities
Tarek Abbas,Anindya Dutta +1 more
TLDR
This Review focuses on recent advances in the understanding of the regulation of p21 and its biological functions with emphasis on its p53-independent tumour suppressor activities and paradoxical tumour-promoting activities, and their implications in cancer.Abstract:
One of the main engines that drives cellular transformation is the loss of proper control of the mammalian cell cycle. The cyclin-dependent kinase inhibitor p21 (also known as p21WAF1/Cip1) promotes cell cycle arrest in response to many stimuli. It is well positioned to function as both a sensor and an effector of multiple anti-proliferative signals. This Review focuses on recent advances in our understanding of the regulation of p21 and its biological functions with emphasis on its p53-independent tumour suppressor activities and paradoxical tumour-promoting activities, and their implications in cancer.read more
Citations
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Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation.
TL;DR: An update on canonical and non-canonical miRNA biogenesis pathways and various mechanisms underlying miRNA-mediated gene regulations and the current knowledge of the dynamics of miRNA action and of the secretion, transfer, and uptake of extracellular miRNAs is provided.
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The cytoprotective role of the Keap1–Nrf2 pathway
TL;DR: Cross-talks with other signalling pathways broadens the role of the Keap1–Nrf2 pathway in determining the fate of the cell, impacting fundamental biological processes such as proliferation, apoptosis, angiogenesis and metastasis.
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Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage.
TL;DR: This review will focus on the multiple functions of p21 in cell cycle regulation, apoptosis and gene transcription after DNA damage and briefly discuss the pathways and factors that have critical roles in p21 expression and activity.
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How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression?
Brandon J. Aubrey,Gemma L. Kelly,Gemma L. Kelly,Ana Janic,Ana Janic,Marco J Herold,Marco J Herold,Andreas Strasser,Andreas Strasser +8 more
TL;DR: Current understanding of the mechanisms by which p53 induces cell death is discussed and how this affects p53-mediated tumour suppression and the response of malignant cells to anticancer therapy is discussed.
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Census and evaluation of p53 target genes.
TL;DR: In this paper, a survey of p53 target genes is presented, and the results show that high-confidence p53 targets are involved in multiple cellular responses, including cell cycle arrest, DNA repair, apoptosis, metabolism, autophagy, mRNA translation and feedback mechanisms.
References
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WAF1, a potential mediator of p53 tumor suppression
Wafik S. El-Deiry,Takashi Tokino,Victor E. Velculescu,Daniel B. Levy,Ramon Parsons,Jeffrey M. Trent,D Lin,W. Edward Mercer,Kenneth W. Kinzler,Bert Vogelstein +9 more
TL;DR: A gene is identified, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line and that could be an important mediator of p53-dependent tumor growth suppression.
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Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Lawrence A. Donehower,Michele Harvey,Betty L. Slagle,Mark J. McArthur,Charles A. Montgomery,Janet S. Butel,Allan Bradley +6 more
TL;DR: Observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.
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Cell cycle, CDKs and cancer: a changing paradigm
TL;DR: Genetic evidence suggests that tumour cells may also require specific interphase CDKs for proliferation, and selective CDK inhibition may provide therapeutic benefit against certain human neoplasias.
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Requirement for p53 and p21 to Sustain G2 Arrest After DNA Damage
Fred Bunz,A. Dutriaux,Christoph Lengauer,Todd Waldman,Shibin Zhou,J. P. Brown,John M. Sedivy,Kenneth W. Kinzler,Bert Vogelstein +8 more
TL;DR: After DNA damage, many cells appear to enter a sustained arrest in the G2 phase of the cell cycle but this arrest could be sustained only when p53 was present in the cell and capable of transcriptionally activating the cyclin-dependent kinase inhibitor p21.
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Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
Chu-Xia Deng,Chu-Xia Deng,Pumin Zhang,J. Wade Harper,Stephen J. Elledge,Stephen J. Elledge,Philip Leder,Philip Leder +7 more
TL;DR: The results establish the role of p21CIP1/WAF1 in the G1 checkpoint, but suggest that the anti-apoptotic and theAnti-oncogenic effects of p53 are more complex.