RT Journal Article
T1 Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions
A1 Cordani, Marco
A1 Garufi, Alessia
A1 Benedetti, Rossella
A1 Tafani, Marco
A1 Aventaggiato, Michele
A1 D’Orazi, Gabriella
A1 Cirone, Mara
AB The p53 protein is the master regulator of cellular integrity, primarily due to its tumor-suppressing functions. Approximately half of all human cancers carry mutations in the TP53 gene, which not only abrogate the tumor-suppressive functions but also confer p53 mutant proteins with oncogenic potential. The latter is achieved through so-called gain-of-function (GOF) mutations that promote cancer progression, metastasis, and therapy resistance by deregulating transcriptional networks, signaling pathways, metabolism, immune surveillance, and cellular compositions of the microenvironment. Despite recent progress in understanding the complexity of mutp53 in neoplastic development, the exact mechanisms of how mutp53 contributes to cancer development and how they escape proteasomal and lysosomal degradation remain only partially understood. In this review, we address recent findings in the field of oncogenic functions of mutp53 specifically regarding, but not limited to, its implications in metabolic pathways, the secretome of cancer cells, the cancer microenvironment, and the regulating scenarios of the aberrant proteasomal degradation. By analyzing proteasomal and lysosomal protein degradation, as well as its connection with autophagy, we propose new therapeutical approaches that aim to destabilize mutp53 proteins and deactivate its oncogenic functions, thereby providing a fundamental basis for further investigation and rational treatment approaches for TP53-mutated cancers.
PB MDP
SN 2218-273X
YR 2024
FD 2024
LK https://hdl.handle.net/20.500.14352/118713
UL https://hdl.handle.net/20.500.14352/118713
LA eng
NO Cordani, M.; Garufi, A.; Benedetti, R.; Tafani, M.; Aventaggiato, M.; D’Orazi, G.; Cirone, M. Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions. Biomolecules 2024, 14, 649. https:// doi.org/10.3390/biom14060649
NO Marco Cordani was supported by grant RYC2021-031003I funded by MICIU/AEI/10.13039/501100011033 and, by European Union NextGenerationEU/PRTR. Marco Tafani was supported by grant Ateneo 2023 from Sapienza University. Mara Cirone was funded by the Italian Association for Cancer Research (AIRC; grant IG 2019-23040).
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO European Commission
NO Sapienza Università di Roma
NO Italian Association for Cancer Research
DS Docta Complutense
RD 9 abr 2025