Advertisement

Topics

Intrinsically disordered domain of tumor suppressor p53 facilitates target search by ultrafast transfer between different DNA strands.

08:00 EDT 9th July 2018 | BioPortfolio

Summary of "Intrinsically disordered domain of tumor suppressor p53 facilitates target search by ultrafast transfer between different DNA strands."

Intersegmental transfer (IST) is an important strategy in the target search used by sequence-specific DNA-binding proteins (DBPs), enabling DBPs to search for targets between multiple DNA strands without dissociation. We examined the IST of the tumor suppressor p53 using ensemble stopped-flow and single-molecule fluorescence measurements. The ensemble measurements demonstrated that p53 exhibits very fast IST, whose rate constant was ∼108 M-1 s-1. To determine the domains of p53 responsible for IST, two mutants with deletions of one of its two DNA binding domains were generated. The mutant lacking the disordered C-terminal (CT) domain (the CoreTet mutant) abolished IST, whereas the mutant lacking the structured core domain (the TetCT mutant) maintained IST, clearly demonstrating the importance of the CT domain. Single-molecule fluorescence measurements further demonstrated the transfer of p53 between two tethered DNA strands. The pseudo-wild-type p53 and the TetCT mutant showed significant transfer efficiencies, whereas the transfer efficiency for the CoreTet mutant was zero. These results suggest that ultrafast IST might be promoted by four copies of the CT domain, by binding to two DNA strands simultaneously. Such ultrafast IST might be important to avoid nearby-bound DBPs during the target search process of p53 in nucleus.

Affiliation

Journal Details

This article was published in the following journal.

Name: Nucleic acids research
ISSN: 1362-4962
Pages:

Links

DeepDyve research library

PubMed Articles [16822 Associated PubMed Articles listed on BioPortfolio]

Conformational Ensemble and Biological Role of the TCTP Intrinsically Disordered Region: Influence of Calcium and Phosphorylation.

The translationally controlled tumor protein (TCTP) is a multifunctional protein that may interact with many other bio-mole-cules, including itself. The experimental determinations of TCTP structure r...

Order within a Disordered Structure.

The transcriptional activity of the androgen receptor is tightly regulated by an intrinsically disordered N-terminal transactivation domain. In this issue of Structure, De Mol et al. (2018) identify ...

MINAR1 is a Notch2-binding protein that inhibits angiogenesis and breast cancer growth.

Intrinsically disordered proteins (IDPs)/intrinsically unstructured proteins (IUPs) are characterized by the lack of fixed or stable tertiary structure, and are increasingly recognized as an important...

Protein Regulation by Intrinsically Disordered Regions: A Role for Subdomains in the IDR of the HIV-1 Rev Protein.

Intrinsically disordered regions (IDRs) in proteins are highly abundant, but they are still commonly viewed as long stretches of polar, solvent accessible residues. Here we show that the disordered C-...

Intrinsically disordered N-terminal domain of the Helicoverpa armigera Ultraspiracle stabilizes the dimeric form via a scorpion-like structure.

Nuclear receptors (NRs) are a family of ligand-dependent transcription factors activated by lipophilic compounds. NRs share a common structure comprising three domains: a variable N-terminal domain (N...

Clinical Trials [7296 Associated Clinical Trials listed on BioPortfolio]

Myeloid Derived Suppressor Cells and Chronic Myeloid Leukemia

The suppression of the immune system creates a permissive environment for development and progression of cancer. One population of immunosuppressive cells that have become the focus of int...

Dependence Receptors and Leukemia

Acute leukaemias (AL) are the first cause of cancer in children, with a majority of B acute lymphoblastic leukemia (ALL) (J. Clavel et al., Eur J Cancer, 2004). Some of the processes causi...

Clinical and Molecular Characterization of Familial Microsatellite Stable Colorectal Cancer

Two major genetic pathways leading to colorectal carcinoma can well be distinguished; the 'suppressor pathway', which is characterized by inactivation of tumor-suppressor genes and the 'mu...

Sleep Disordered Breathing in Patients With Chronic Heart Failure

Only few prospective studies systematically investigated the prevalence of sleep disordered breathing in patients with stable chronic heart failure. Furthermore there is no report on the i...

Assessment of the HIV CNS Reservoir, Neurological and Neuro-cognitive Effects, and Source of Rebound HIV in CNS

This study aims to describe in depth the CNS, CNS HIV reservoir and CNS viral rebound in consenting SEARCH 019 subjects prior to, during and after the SEARCH 019 study intervention (VHM + ...

Medical and Biotech [MESH] Definitions

A nuclear and cytoplasmic protein that associates with KINETOCHORES and contains a C-terminal TUDOR DOMAIN. It plays a critical role in the cellular response to DNA DAMAGE and localizes to DOUBLE-STRAND DNA BREAKS. It may also function in M PHASE CELL CYCLE CHECKPOINTS and as an enhancer of TUMOR SUPPRESSOR PROTEIN P53-mediated transcriptional activation.

A gene product of the p16 tumor suppressor gene (GENES, P16). It antagonizes the function of MDM2 PROTEIN (which regulates P53 TUMOR SUPPRESSOR PROTEIN by targeting it for degradation). p14ARF is produced from the beta mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced alpha transcript, is CYCLIN-DEPENDENT KINASE INHIBITOR P16. Both p16 gene products have tumor suppressor functions.

An E3 UBIQUITIN LIGASE that interacts with and inhibits TUMOR SUPPRESSOR PROTEIN P53. Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF.

Functional proteins that do not have unique, stable, folded, three-dimensional native structures or that possess non-ordered regions under physiological conditions. They are characterized by extraordinary structural flexibility and plasticity, which enable them to adopt different conformations in response to different stimuli or different interactions.

A 34 kDa signal transducing adaptor protein that associates with TUMOR NECROSIS FACTOR RECEPTOR TYPE 1. It facilitates the recruitment of signaling proteins such as TNF RECEPTOR-ASSOCIATED FACTOR 2 and FAS ASSOCIATED DEATH DOMAIN PROTEIN to the receptor complex.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topic

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...


Searches Linking to this Article