p53 positively regulates the proliferation of hepatic progenitor cells promoted by laminin-521

Ma, Mingyang; Hua, Shuyao; Min, Xiangde; Wang, Liang; Li, Jun; Wu, Ping; Liang, Huifang; Zhang, Bixiang; Chen, Xiaoping; Xiang, Shuai

doi:10.1038/s41392-022-01107-7

Cited by 8 publications

(7 citation statements)

References 59 publications

(63 reference statements)

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“…The primary dimer relies on eight backbone hydrogen bonds of the β-sheet and is also stabilized by hydrophobic interactions (Phe328, Leu330, Ile332, Phe338 and Phe341) as well as a salt bridge between Arg337 and Asp352. 35 The dimer-dimer interactions are primarily mediated by hydrophobic contacts (Met340, Phe341, Leu344, Ala347, Leu348 and Leu350). 35 R337C/H/P and L344P affect the formation and transcriptional activity of p53 tetramers and are involved in Li-Fraumeni Syndrome and Li-Fraumeni-Like Syndrome.…”

Section: The Structures Of P53mentioning

confidence: 99%

“… 35 The dimer-dimer interactions are primarily mediated by hydrophobic contacts (Met340, Phe341, Leu344, Ala347, Leu348 and Leu350). 35 R337C/H/P and L344P affect the formation and transcriptional activity of p53 tetramers and are involved in Li-Fraumeni Syndrome and Li-Fraumeni-Like Syndrome. 316 The G334V mutant contributed to a beta-dominated structural transition leading to amyloid formation at physiological temperature.…”

Section: The Structures Of P53mentioning

confidence: 99%

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Targeting p53 pathways: mechanisms, structures, and advances in therapy

Wang

Guo

Wei

et al. 2023

Sig Transduct Target Ther

101

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The TP53 tumor suppressor is the most frequently altered gene in human cancers, and has been a major focus of oncology research. The p53 protein is a transcription factor that can activate the expression of multiple target genes and plays critical roles in regulating cell cycle, apoptosis, and genomic stability, and is widely regarded as the “guardian of the genome”. Accumulating evidence has shown that p53 also regulates cell metabolism, ferroptosis, tumor microenvironment, autophagy and so on, all of which contribute to tumor suppression. Mutations in TP53 not only impair its tumor suppressor function, but also confer oncogenic properties to p53 mutants. Since p53 is mutated and inactivated in most malignant tumors, it has been a very attractive target for developing new anti-cancer drugs. However, until recently, p53 was considered an “undruggable” target and little progress has been made with p53-targeted therapies. 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 p53 protein and its inactivation by oncogenic mutations. In addition, we review the efforts that have been made in p53-targeted therapies, and discuss the challenges that have been encountered in clinical development.

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Section: The Structures Of P53mentioning

confidence: 99%

Section: The Structures Of P53mentioning

confidence: 99%

Targeting p53 pathways: mechanisms, structures, and advances in therapy

Wang

Guo

Wei

et al. 2023

Sig Transduct Target Ther

101

View full text Add to dashboard Cite

show abstract

“…Additionally, LN521 has been found to promote the proliferation of hepatic progenitor cells [22] and contribute to hepatic speci cation in human embryonic stem cell-derived de nite endoderm cells [23]. Furthermore, LN521 also suggested to promote hepatic stellate cell quiescence in rat [24].…”

Section: Discussionmentioning

confidence: 96%

Laminin α5β2γ1 promotes uterine stromal cells' mesenchymal-epithelial transition during decidualization

Wang,

Fu,

Xie

et al. 2023

Preprint

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Decidualization is critical to pregnancy in primates and rodents. Endometrial stromal cells undergo the mesenchymal-epithelial transition to transform into decidual stromal cells to provide nutrition and support vascularization during decidualization. Laminins, as the main component of the epithelial basement membrane, regulate cellular adhesion, growth, migration, and differentiation. Our previous study showed that laminin α5β2γ1 strongly expressed in mouse decidua. However, the regulation and function of laminin α5β2γ1 during endometrium decidualization are still unknown. Here, our study reveals robust expression of laminin α5β2γ1 in mice and artificially induced mice deciduoma. And laminin α5β2γ1 is also upregulated during mice and human in vitro decidualization. We demonstrate that progesterone regulates the expression of laminin α5β2γ1 during in vitro decidualization in mice. Interestingly, coated-laminin α5β2γ1 promotes the mesenchymal-epithelial transition in mouse and human uterine stromal cells.

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“…The viability of the LPCs was analyzed by CCK-8 assays [ 27 ]. Briefly, LPCs were seeded in 96-well plates at 800 cells/100 μl of medium per well.…”

Section: Methodsmentioning

confidence: 99%

TGF-β downstream of Smad3 and MAPK signaling antagonistically regulate the viability and partial epithelial–mesenchymal transition of liver progenitor cells

Sun,

Wu,

et al. 2024

Aging

Self Cite

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Background: Liver progenitor cells (LPCs) are a subpopulation of cells that contribute to liver regeneration, fibrosis and liver cancer initiation under different circumstances. Results: By performing adenoviral-mediated transfection, CCK-8 analyses, F-actin staining, transwell analyses, luciferase reporter analyses and Western blotting, we observed that TGF-β promoted cytostasis and partial epithelial–mesenchymal transition (EMT) in LPCs. In addition, we confirmed that TGF-β activated the Smad and MAPK pathways, including the Erk, JNK and p38 MAPK signaling pathways, and revealed that TGFβ-Smad signaling induced growth inhibition and partial EMT, whereas TGFβ-MAPK signaling had the opposite effects on LPCs. We further found that the activity of Smad and MAPK signaling downstream of TGF-β was mutually restricted in LPCs. Mechanistically, we found that TGF-β activated Smad signaling through serine phosphorylation of both the C-terminal and linker regions of Smad2 and 3 in LPCs. Additionally, TGFβ-MAPK signaling inhibited the phosphorylation of Smad3 but not Smad2 at the C-terminus, and it reinforced the linker phosphorylation of Smad3 at T179 and S213. We then found that overexpression of mutated Smad3 at linker phosphorylation sites intensifies TGF-β-induced cytostasis and EMT, mimicking the effects of MAPK inhibition in LPCs, whereas mutation of Smad3 at the C-terminus caused LPCs to blunt TGF-β-induced cytostasis and partial EMT. Conclusion: These results suggested that TGF-β downstream of Smad3 and MAPK signaling were mutually antagonistic in regulating the viability and partial EMT of LPCs. This antagonism may help LPCs overcome the cytostatic effect of TGF-β under fibrotic conditions and maintain partial EMT and progenitor phenotypes.

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p53 positively regulates the proliferation of hepatic progenitor cells promoted by laminin-521

Cited by 8 publications

References 59 publications

Targeting p53 pathways: mechanisms, structures, and advances in therapy

Targeting p53 pathways: mechanisms, structures, and advances in therapy

Laminin α5β2γ1 promotes uterine stromal cells' mesenchymal-epithelial transition during decidualization

TGF-β downstream of Smad3 and MAPK signaling antagonistically regulate the viability and partial epithelial–mesenchymal transition of liver progenitor cells

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