Targeting p53 pathways: mechanisms, structures and advances in …
2023年3月1日 · Here, we provide a systematic review of the diverse molecular mechanisms of the p53 signaling pathway and how TP53 mutations impact tumor progression. We also discuss key structural features of...
The Tumor Suppressor p53: From Structures to Drug Discovery
Here, we discuss key structural aspects of p53 function and its inactivation by oncogenic mutations. Concerted action of folded and intrinsically disordered domains of the highly dynamic p53 protein provides binding promiscuity and specificity, allowing p53 to process a myriad of cellular signals to maintain the integrity of the human genome.
Structural insight into the molecular mechanism of p53
2021年4月16日 · Here, we report a 2.5 Å crystal structure of human p53/BCL-xL complex. In this structure, two p53 molecules interact as a homodimer, and bind one BCL-xL molecule to form a ternary complex with...
Tumor Suppressor p53: Biology, Signaling Pathways, and …
TP53 is a gene that encodes for the p53 tumor suppressor protein, commonly referred to as the “Guardian of the Genome” [1]. Its main biological function appears to involve the protection of the DNA integrity of the cell. TP53 plays additional roles …
An Integrated View of p53 Dynamics, Function, and Reactivation
The tumor suppressor p53 plays a vital role in responding to cell stressors such as DNA damage, hypoxia, and tumor formation by inducing cell-cycle arrest, senescence, or apoptosis. ... DNA is depicted in light blue surface representation while NTD, DBD, TET and CTD domains of one fl-p53 monomer are highlighted in orange, pink, purple and green ...
Toward Cancer Diagnostics of the Tumor Suppressor p53 by Surface …
2020年12月14日 · The tumor suppressor p53 protein plays a crucial role in many biological processes. The presence of abnormal concentrations of wild-type p53, or some of its mutants, can be indicative of a pathological cancer state. p53 represents therefore a valuable biomarker for tumor screening approaches and dev …
Cell Surface Trafficking of Fas: A Rapid Mechanism of p53
1998年10月9日 · In human vascular smooth muscle cells, p53 activation transiently increased surface Fas (CD95) expression by transport from the Golgi complex. Golgi disruption blocked both p53-induced surface Fas expression and apoptosis. p53 also induced Fas-FADD binding and transiently sensitized cells to Fas-induced apoptosis.
An integrated view of p53 dynamics, function, and reactivation
2021年1月2日 · DNA is depicted in light blue surface representation while NTD, DBD, TET and CTD domains of one fl-p53 monomer are highlighted in orange, pink, purple and green surface representation, respectively. Methods that can identify correlated motions and allosteric communication in protein structures can be extremely helpful for the interpretation of ...
Structure of the p53/RNA polymerase II assembly - PubMed
2021年3月25日 · The transactivation domain of p53 binds the surface of Pol II's jaw that contacts downstream DNA. These findings suggest that p53's functional domains directly regulate DNA binding activity of Pol II to mediate transcription, thereby providing insights into p53-regulated gene expression.
Mutant p53 in cancer: from molecular mechanism to therapeutic ...
2022年11月18日 · Emerging evidence suggests that mutp53 is highly associated with advanced malignancies and poor prognosis, which makes it a target for development of novel cancer therapies. Herein, we provide a...