p53 Plays a Role in Mesenchymal Differentiation Programs, in a Cell Fate Dependent Manner
Alina Molchadsky,Igor Shats,Naomi Goldfinger,Meirav Pevsner-Fischer,Melissa V. Olson,Ariel Rinon,Eldad Tzahor,Guillermina Lozano,Dov Zipori,Rachel Sarig,Varda Rotter +10 more
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TL;DR: P53 down-regulated the expression of master differentiation-inducing transcription factors, thereby inhibiting osteogenic, adipogenic and smooth muscle differentiation of multiple mesenchymal cell types, and thus can be referred as a “guardian of differentiation” at large.
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Abstract: Background The tumor suppressor p53 is an important regulator that controls various cellular networks, including cell differentiation. Interestingly, some studies suggest that p53 facilitates cell differentiation, whereas others claim that it suppresses differentiation. Therefore, it is critical to evaluate whether this inconsistency represents an authentic differential p53 activity manifested in the various differentiation programs. Methodology/Principal Findings To clarify this important issue, we conducted a comparative study of several mesenchymal differentiation programs. The effects of p53 knockdown or enhanced activity were analyzed in mouse and human mesenchymal cells, representing various stages of several differentiation programs. We found that p53 down-regulated the expression of master differentiation-inducing transcription factors, thereby inhibiting osteogenic, adipogenic and smooth muscle differentiation of multiple mesenchymal cell types. In contrast, p53 is essential for skeletal muscle differentiation and osteogenic re-programming of skeletal muscle committed cells. Conclusions These comparative studies suggest that, depending on the specific cell type and the specific differentiation program, p53 may exert a positive or a negative effect, and thus can be referred as a “guardian of differentiation” at large.
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Citations
Mutations in the p53 Tumor Suppressor Gene: Important Milestones at the Various Steps of Tumorigenesis
TL;DR: Interestingly, mutations in the p53 gene were shown to occur at different phases of the multistep process of malignant transformation, thus contributing differentially to tumor initiation, promotion, aggressiveness, and metastasis.
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p53 at a glance
TL;DR: The role of the p53 protein in cancer has been studied intensively as mentioned in this paper, and p53 is a crucial tumor suppressor, long recognized to suppress cancer through the induction of cell-cycle-arrest or apoptosis programs in response to a plethora of different threats.
Adipogenesis at a glance.
TL;DR: The formation of adipocytes from precursor stem cells involves a complex and highly orchestrated programme of gene expression and the basic network of transcription factors that regulates adipogenesis has remained remarkably unchanged in recent years.
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p53 and MicroRNA-34 Are Suppressors of Canonical Wnt Signaling
Nam Hee Kim,Hyun Sil Kim,Nam-Gyun Kim,Inhan Lee,Hyung Seok Choi,Xiao Yan Li,Shi Eun Kang,So Young Cha,Joo Kyung Ryu,Jung Min Na,Changbum Park,Kunhong Kim,Sanghyuk Lee,Sanghyuk Lee,Barry M. Gumbiner,Jong In Yook,Stephen J. Weiss +16 more
TL;DR: P53 transactivated microRNA-34 (miR-34), which consequently suppressed the transcriptional activity of β-catenin–T cell factor and lymphoid enhancer factor (TCF/LEF) complexes by targeting the untranslated regions (UTRs) of a set of conserved targets in a network of genes encoding elements of the Wnt pathway.
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LncRNA CAIF inhibits autophagy and attenuates myocardial infarction by blocking p53-mediated myocardin transcription
Cuiyun Liu,Yuhui Zhang,Rui-Bei Li,Zhou Luyu,Tao An,Rongcheng Zhang,Mei Zhai,Yan Huang,Kaowen Yan,Yanhan Dong,Murugavel Ponnusamy,Chan Shan,Sheng Xu,Qi Wang,Yan-Hui Zhang,Jian Zhang,Kun Wang +16 more
TL;DR: The authors identify lncCAIF, and show that it suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53 -mediated transcription of myocardin.
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