■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis

The protein kinase ataxia-telangiectasia mutated (ATM) is best known for its role as an apical activator of the DNA damage response in the face of DNA double-strand breaks (DSBs). Following induction of DSBs, ATM mobilizes one of the most extensive signalling networks that responds to specific stimuli and modifies directly or indirectly a broad range of targets. Although most ATM research has focused on this function, evidence suggests that ATM-mediated phosphorylation has a role in the response to other types of genotoxic stress. Moreover, it has become apparent that ATM is active in other cell signalling pathways involved in maintaining cellular homeostasis.

The ATM protein kinase: regulating the cellular response to genotoxic stress, and more

Akt in cancer: Mediator and more.

For many years, transcription factor Sp1 was viewed as a basal transcription factor and relegated to a role in the regulation of so-called housekeeping genes. Identification of Sp1's role in recruiting the general transcription machinery in the absence of a TATA box increased its importance in gene regulation, particularly in light of recent estimates that the majority of mammalian genes lack a TATA box. In this review, we briefly consider the history of Sp1, the founding member of the Sp family of transcription factors. We review the evidence suggesting that Sp1 is highly regulated by post-translational modifications that positively and negatively affect the activity of Sp1 on a wide array of genes. Sp1 is over-expressed in many cancers and is associated with poor prognosis. Targeting Sp1 in cancer treatment has been suggested; however, our review of the literature on the role of Sp1 in the regulation of genes that contribute to the 'hallmarks of cancer' illustrates the extreme complexity of Sp1 functions. Sp1 both activates and suppresses the expression of a number of essential oncogenes and tumor suppressors, as well as genes involved in essential cellular functions, including proliferation, differentiation, the DNA damage response, apoptosis, senescence and angiogenesis. Sp1 is also implicated in inflammation and genomic instability, as well as epigenetic silencing. Given the apparently opposing effects of Sp1, a more complete understanding of the function of Sp1 in cancer is required to validate its potential as a therapeutic target.

https://febs.onlinelibrary.wiley.com/doi/epdf/10.1111/febs.13148

Sp1 and the ‘hallmarks of cancer’

http://digital.csic.es/bitstream/10261/124679/1/PharTher%282015%29.pdf

Sp1 transcription factor: A long-standing target in cancer chemotherapy.

Sp1 is a ubiquitously expressed transcription factor that is phosphorylated by ataxia telangiectasia mutated kinase (ATM) in response to ionizing radiation and H(2)O(2). Here, we show by indirect immunofluorescence that Sp1 phosphorylated on serine 101 (pSp1) localizes to ionizing radiation-induced foci with phosphorylated histone variant γH2Ax and members of the MRN (Mre11, Rad50, and Nbs1) complex. More precise analysis of occupancy of DNA double-strand breaks (DSBs) by chromatin immunoprecipitation (ChIP) shows that Sp1, like Nbs1, resides within 200 bp of DSBs. Using laser microirradiation of cells, we demonstrate that pSp1 is present at DNA DSBs by 7.5 min after induction of damage and remains at the break site for at least 8 h. Depletion of Sp1 inhibits repair of site-specific DNA breaks, and the N-terminal 182-amino-acid peptide, which contains targets of ATM kinase but lacks the zinc finger DNA binding domain, is phosphorylated, localizes to DSBs, and rescues the repair defect resulting from Sp1 depletion. Together, these data demonstrate that Sp1 is rapidly recruited to the region immediately adjacent to sites of DNA DSBs and is required for DSB repair, through a mechanism independent of its sequence-directed transcriptional effects.

Sp1 facilitates DNA double-strand break repair through a nontranscriptional mechanism

Roles of ChlR1 DNA helicase in replication recovery from DNA damage

Transcription Factor Sp1 Promotes Chromatin Remodeling at DNA Double‐Strand Breaks

Sp1-dependent recruitment of the histone acetylase p300 to DSBs facilitates chromatin remodeling and recruitment of the NHEJ repair factor Ku70.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Kate Beishline

Author Tools

Chat about Author