Jul 2026· Cell Death and Differentiation· 0 citations· 31 references
Medicine
TL;DR
This perspective brings together multiple observations concerning the regulatory architecture and functional interactions of the TP53 gene and its isoforms to cooperate to maintain an open chromatin state in the P2 region in a manner reminiscent of a neural "associative memory" network.
Abstract
This perspective brings together multiple observations concerning the regulatory architecture and functional interactions of the TP53 gene and its isoforms. The TP53 gene encompasses an internal enhancer-promoter region (P2) located between exons 2 and 5, which is transactivated by full-length TAp53α, to drive the expression of truncated TP53 isoforms ΔN133p53α, β or γ. ΔN133p53α homo-monomers or dimers very likely form hetero-tetramers with homo-dimers of full-length TAp53α. The TAp53α-ΔN133p53 tetramer then acts as a transcription factor augmenting mitochondrial efficiency, DNA repair, telomere restoration and reversing cellular senescence, thus opposing many outputs of tumor suppressive TAp53α homo-tetramers. Other transcription factors, such as estrogen receptor (ER), OCT1, and SOX9 also may bind the P2 promoter-enhancer to promote transcription of oncogenic TP53 isoforms. These transcription factors, together with full-length TAp53α, appear to cooperate to maintain an open chromatin state in the P2 region in a manner reminiscent of a neural "associative memory" network.
An integrated overview of the molecular features and functional roles of BAP1 is provided, with particular emphasis on its impacts on the regulation of cell death including apoptosis, ferroptosis and disulfidptosis.
Kexin Fan, Jun Yao, Shaobo Wu et al.· Frontiers in Cell and Develo...· 0 citations
This study uncovers a therapeutic vulnerable lncRNA-centric circuitry and provides compelling preclinical evidence for the development and application of a novel RNA targeting-LNP based therapy for treatment of myeloid leukemia.
Zhenggen Jin, Brendan D. Ma, Karen Y. T. Chan et al.· bioRxiv· 0 citations
The tumor suppressor p53 plays a crucial role in preventing cancer development, and its dysfunction is frequently observed in various cancers. This study identifies a novel regulatory interaction between p53 and ITM2A. We found that p53 upregulates ITM2A expression, while ITM2A in turn inhibits p53 function, suggesting a negative feedback loop. ITM2A mRNA levels were reduced across multiple tumor types, particularly in those harboring mutant p53, and low ITM2A expression correlated with poor patient survival. Mechanistically, ITM2A physically interacts with p53, selectively modulates its phosphorylation (reducing Ser392 while enhancing Ser37), and promotes cytoplasmic accumulation of p53. These modifications collectively suppress p53-dependent transcription, an effect consistently observed across multiple cell lines under both basal conditions and upon physiological p53 activation by genotoxic stress. Conversely, ITM2A depletion enhances p53 nuclear accumulation and transcriptional activity. These findings reveal a novel autoregulatory circuit wherein p53 induces ITM2A expression, which then attenuates p53 activity, suggesting ITM2A as a potential prognostic marker and therapeutic target for cancers with dysregulated p53 signaling.
Sim Namkoong, Minsu Jang, Jeong‐In Lee et al.· Cell Cycle· 0 citations
This review summarizes current knowledge regarding the molecular biology of TTP and HuR, emphasizing their opposing functions in mRNA metabolism and cancer progression; discusses mechanisms regulating their expression, localization, phosphorylation, and RNA-binding activity; analyze cancer-specific evidence; and examines models in which both proteins are co-expressed or functionally interconnected.
R. Lotti, Tommaso Selmi, Alexis Grande et al.· Frontiers in Oncology· 0 citations
These findings establish CTD-2566 J3.1 as a multifunctional enhancer-associated lncRNA (e-lncRNA) that orchestrates key oncogenic processes in luminal breast cancer and underscores the utility of three-dimensional culture systems to reveal context-specific lncRNA functions.
Stephanie I. Nuñez-Olvera, L. R. Hernández-Barrientos, Elia Martínez-Baeza et al.· International Journal of Bio...· 0 citations
Insight is provided into IRES-mediated translation of Δ160p53, which can be considered a novel target for cancer treatment and its role in cancer regulation.
P. K. Ghosh, Piyanki Das, Sahana Ghosh et al.· bioRxiv· 0 citations
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