A chimeric p53 cDNA was constructed so that the fragment coding for 39 residues of the chicken p53 tetramerization domain replaced the corresponding region of human p53. The chimeric cDNA substantially inhibited the colony-forming ability of transfected human and mouse cells, suggesting a suppressory potential for its product. The chimeric p53 activated promoters containing p53-responsive elements. In contrast to wild-type human p53, the chimeric p53 remained capable of transcription activation in the presence of dominant-negative mutant p53-His175. This makes the chimeric p53 a convenient model for elaborating gene therapy protocols for tumors with dominant-negative p53 forms. The chimeric p53 may be used to study the role of transdominance of p53 mutants in carcinogenesis and the interactions of p53 with related transcription factors (p73, p63).
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J Am Chem Soc
January 2025
Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
PROTACs have emerged as a therapeutic modality for the targeted degradation of proteins of interest (POIs). Central to PROTAC technology are the E3 ligase recruiters, yet only a few of them have been identified due to the lack of ligandable pockets in ligases, especially among single-subunit ligases. We propose that binders of partner proteins of single-subunit ligases could be repurposed as new ligase recruiters.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Pharmacological reactivation of the tumor suppressor p53 remains a key challenge for the treatment of cancer. Acetylation Targeting Chimera (AceTAC), a novel technology is previously reported that hijacks lysine acetyltransferases p300/CBP to acetylate the p53Y220C mutant. However, p300/CBP are the only acetyltransferases harnessed for AceTAC development to date.
View Article and Find Full Text PDFHematology Am Soc Hematol Educ Program
December 2024
Department of Hematology and Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY.
TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) remain a challenging spectrum of clonal myeloid disease with poor prognosis. Recent studies have shown that in AML, MDS, and MDS/AML with biallelic TP53 loss, the TP53-mutated clone becomes dominant. These are highly aggressive diseases that are resistant to most chemotherapies.
View Article and Find Full Text PDFCell Rep Med
December 2024
Technical University of Munich (TUM), School of Medicine and Health, Department of Preclinical Medicine, Institute for Medical Microbiology, Immunology and Hygiene, 81675 Munich, Germany; TUM, Institute for Advanced Study, 85748 Garching, Germany. Electronic address:
ACS Omega
November 2024
School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255000, China.
The tumor suppressor protein p53 is among the most commonly mutated proteins across a variety of cancer types. Notably, the p53 R175H mutation ranks as one of the most prevalent hotspot mutations. Proteolysis-targeting chimeras (PROTACs) represent a class of bifunctional molecules capable of harnessing the cellular ubiquitin-proteasome pathway to facilitate targeted protein degradation.
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