Loss of p16: A Bouncer of the Immunological Surveillance?

p16INK4A (hereafter called p16) is an important tumor suppressor protein frequently suppressed in human cancer and highly upregulated in many types of senescence. Although its role as a cell cycle regulator is very well delineated, little is known about its other non-cell cycle-related roles. Importantly, recent correlative studies suggest that p16 may be a regulator of tissue immunological surveillance through the transcriptional regulation of different chemokines, interleukins and other factors secreted as part of the senescence-associated secretory phenotype (SASP). Here, we summarize the current evidence supporting the hypothesis that p16 is a regulator of tumor immunity.

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Cytoplasmic chromatin fragments—from mechanisms to therapeutic potential

eLife ◽

10.7554/elife.63728 ◽

2021 ◽

Vol 10 ◽

Author(s):

Karl N Miller ◽

Nirmalya Dasgupta ◽

Tianhui Liu ◽

Peter D Adams ◽

Maria Grazia Vizioli

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Chronic Diseases ◽

Functional Role ◽

Therapeutic Potential ◽

Tissue Homeostasis ◽

Current Evidence ◽

Nuclear Chromatin ◽

Acute Responses ◽

Secretory Phenotype

Senescent cells, damaged cells that permanently exit the cell cycle, play important roles in development, tissue homeostasis, and tumorigenesis. Although many of these roles are beneficial in acute responses to stress and damage, the persistent accumulation of senescent cells is associated with many chronic diseases through their proinflammatory senescence-associated secretory phenotype (SASP). SASP expression is linked to DNA damage; however, the mechanisms that control the SASP are incompletely understood. More recently, it has been shown that senescent cells shed fragments of nuclear chromatin into the cytoplasm, so called cytoplasmic chromatin fragments (CCF). Here, we provide an overview of the current evidence linking DNA damage to the SASP through the formation of CCF. We describe mechanisms of CCF generation and their functional role in senescent cells, with emphasis on therapeutic potential.

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MCMs in Cancer: Prognostic Potential and Mechanisms

Analytical Cellular Pathology ◽

10.1155/2020/3750294 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Si Yu ◽

Guanqun Wang ◽

Yue Shi ◽

Haifeng Xu ◽

Yongchang Zheng ◽

...

Keyword(s):

Cell Cycle ◽

Replication Initiation ◽

Current Evidence ◽

Future Research ◽

Hallmarks Of Cancer ◽

Minichromosome Maintenance ◽

Proliferation Markers ◽

A Cell ◽

Underlying Mechanisms ◽

Insight Into

Enabling replicative immortality and uncontrolled cell cycle are hallmarks of cancer cells. Minichromosome maintenance proteins (MCMs) exhibit helicase activity in replication initiation and play vital roles in controlling replication times within a cell cycle. Overexpressed MCMs are detected in various cancerous tissues and cancer cell lines. Previous studies have proposed MCMs as promising proliferation markers in cancers, while the prognostic values remain controversial and the underlying mechanisms remain unascertained. This review provides an overview of the significant findings regarding the cellular and tumorigenic functions of the MCM family. Besides, current evidence of the prognostic roles of MCMs is retrospectively reviewed. This work also offers insight into the mechanisms of MCMs prompting carcinogenesis and adverse prognosis, providing information for future research. Finally, MCMs in liver cancer are specifically discussed, and future perspectives are provided.

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Nuclear pore density controls heterochromatin reorganization during senescence

10.1101/374033 ◽

2018 ◽

Author(s):

Charlene Boumendilrid ◽

Priya Hari ◽

Karl C. F. Olsen ◽

Juan Carlos Acosta ◽

Wendy A. Bickmore

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Tumour Progression ◽

Nuclear Periphery ◽

Nuclear Pore ◽

Pore Density ◽

Cycle Arrest ◽

A Cell ◽

Secretory Phenotype

AbstractOncogene induced senescence (OIS) is a cell cycle arrest program triggered by oncogenic signalling. An important characteristic of OIS is activation of the senescence associated secretory phenotype (SASP)1 which can reinforce cell cycle arrest, lead to paracrine senescence but also promote tumour progression2–4. Concomitant with cell cycle arrest and the SASP activation, OIS cells undergo a striking nuclear chromatin reorganization, with loss of heterochromatin from the nuclear periphery and the appearance of internal senescence-associated heterochromatin foci (SAHF)5. The mechanisms by which SAHF are formed, and their role in cell cycle arrest and expression of the SASP, remain poorly understood. Here we show that nuclear pore density increases during OIS and is responsible for SAHF formation. In particular, we show that the nucleoporin TPR is required for both SAHF formation and maintenance. The TPR-induced loss of SAHF does not affect cell cycle arrest but completely abrogates the SASP. Our results uncover a previously unknown role of nuclear pores in heterochromatin reorganization in mammalian nuclei and in senescence, which uncouples the cell cycle arrest from the SASP.

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