Estrogen receptors and E2F transcription factors are the key players of two nuclear signaling pathways which exert a major role in oncogenesis, particularly in the mammary gland. Different levels of dialogue between t...Estrogen receptors and E2F transcription factors are the key players of two nuclear signaling pathways which exert a major role in oncogenesis, particularly in the mammary gland. Different levels of dialogue between these two pathways have been deciphered and deregulation of the E2F pathway has been shown to impact the response of breast cancer cells to endocrine therapies. The present review focuses on the transcriptional coregulator RIP140/NRIP1 which is involved in several regulatory feed-back loops and inhibitory cross-talks between different nuclear signaling pathways. RIP140 regulates the transactivation potential of estrogen receptors and E2Fs and is also a direct transcriptional target of these transcription factors. Published data highlight the complex regulation of RIP140 expression at the transcriptional level and its potential role in transcription cross-talks. Indeed, a subtle regulation of RIP140 expression levels has important consequences on other transcription networks targeted by this coregulator. Another level of regulation implies titration mechanisms by which activation of a pathway leads to sequestration of the RIP140 protein and thus impinges other gene regulatory circuitries. Altogether, RIP140 occupies a place of choice in the dialogue between nuclear receptors and E2Fs, which could be highly relevant in various human pathologies such as cancer or metabolic diseases.展开更多
The E2F family of transcription factors is crucial for cell cycle progression and cell fate decisions.Although E2Fs have been widely studied in mammals,there have been few studies performed in insects.Here,we determin...The E2F family of transcription factors is crucial for cell cycle progression and cell fate decisions.Although E2Fs have been widely studied in mammals,there have been few studies performed in insects.Here,we determined the function of E2F4 in the silkworm,Bombyx mori.We demonstrate that E2F proteins are highly conserved among species from lower animals to higher mammals.Overexpression of the BmE2F4 gene led to cell cycle arrest in the G1 phase,whereas interfering with the BmE2F4 mRNA led to accumulation of cells in the S phase.These results indicate that BmE2F4 is important in cell cycle regulation.We also demonstrate that the BmE2F4 gene is involved in DNA replication of BmN-SWU1 cells and DNA synthesis in the silk gland.Furthermore,we identified a protein called Bm14-3-3ζthat can interact with BmE2F4 and allow it to localize in the nucleus.Overexpression of the Bm14-3-3ζgene led to cell cycle arrest in the G1 phase,while knocking down the gene increased the proportion of cells in S phase.These findings provide important insights into the function of E2F transcription factors and increase our understanding of their involvement in cell cycle regulation.展开更多
The E2F/DP pathway is a widely conserved regulatory mechanism in pluricellular organisms.The family of E2F and DP transcription factors was originally described having a role in the transition from the G1 to the S pha...The E2F/DP pathway is a widely conserved regulatory mechanism in pluricellular organisms.The family of E2F and DP transcription factors was originally described having a role in the transition from the G1 to the S phase of the cell cycle.However,the discovery of hundreds of possible gene targets and their involvement in many other biochemical processes,soon showed that they participated in cell development and differentiation,chromatin remodeling,DNA repair and others.The E2F/DP transcription factors can act as either activators or repressors of transcription depending on their association to other regulatory proteins,particularly the retinoblastoma protein,or even depending to their protein structure that can define their role.In plants the E2F/DP pathway also regulates endoreduplication,a process present along the life cycle,from organ elongation to root differentiation and reproduction.These transcription factors also help plant cells to respond to environmental disturbances such as those caused by different types of radiation,or by pathogens.This review focuses on the“so called”non-canonical functions of the E2F/DP family proteins in animal and plant cells,that are in fact essential activities that connect regulatory circuits among multiple metabolic pathways by means of their atypical functions.展开更多
文摘Estrogen receptors and E2F transcription factors are the key players of two nuclear signaling pathways which exert a major role in oncogenesis, particularly in the mammary gland. Different levels of dialogue between these two pathways have been deciphered and deregulation of the E2F pathway has been shown to impact the response of breast cancer cells to endocrine therapies. The present review focuses on the transcriptional coregulator RIP140/NRIP1 which is involved in several regulatory feed-back loops and inhibitory cross-talks between different nuclear signaling pathways. RIP140 regulates the transactivation potential of estrogen receptors and E2Fs and is also a direct transcriptional target of these transcription factors. Published data highlight the complex regulation of RIP140 expression at the transcriptional level and its potential role in transcription cross-talks. Indeed, a subtle regulation of RIP140 expression levels has important consequences on other transcription networks targeted by this coregulator. Another level of regulation implies titration mechanisms by which activation of a pathway leads to sequestration of the RIP140 protein and thus impinges other gene regulatory circuitries. Altogether, RIP140 occupies a place of choice in the dialogue between nuclear receptors and E2Fs, which could be highly relevant in various human pathologies such as cancer or metabolic diseases.
基金We thank Dr.Jiangbo Song for phylogenetic analysis.This research was funded by National Natural Science Foundation of China(31872428 and 31872427)Natural Science Foundation of Chongqing(cstc2019jcyj-msxmX0096 and estc 2020jscx-msxmX0045)China Agriculture Research System(CARS-18).
文摘The E2F family of transcription factors is crucial for cell cycle progression and cell fate decisions.Although E2Fs have been widely studied in mammals,there have been few studies performed in insects.Here,we determined the function of E2F4 in the silkworm,Bombyx mori.We demonstrate that E2F proteins are highly conserved among species from lower animals to higher mammals.Overexpression of the BmE2F4 gene led to cell cycle arrest in the G1 phase,whereas interfering with the BmE2F4 mRNA led to accumulation of cells in the S phase.These results indicate that BmE2F4 is important in cell cycle regulation.We also demonstrate that the BmE2F4 gene is involved in DNA replication of BmN-SWU1 cells and DNA synthesis in the silk gland.Furthermore,we identified a protein called Bm14-3-3ζthat can interact with BmE2F4 and allow it to localize in the nucleus.Overexpression of the Bm14-3-3ζgene led to cell cycle arrest in the G1 phase,while knocking down the gene increased the proportion of cells in S phase.These findings provide important insights into the function of E2F transcription factors and increase our understanding of their involvement in cell cycle regulation.
基金This work was supported by Consejo Nacional de Ciencia y Tecnología[Grant No.CB220661,PostgraduateMobility grants to V.A.S.C.and SNI III grant to S.R.R.]and Universidad Nacional Autónoma de México[DGAPA-PAPIIT IN215316,PAIP 5000-9124,PAIP 5000-9130 and PAEP-UNAM grant to V.A.S.C.].
文摘The E2F/DP pathway is a widely conserved regulatory mechanism in pluricellular organisms.The family of E2F and DP transcription factors was originally described having a role in the transition from the G1 to the S phase of the cell cycle.However,the discovery of hundreds of possible gene targets and their involvement in many other biochemical processes,soon showed that they participated in cell development and differentiation,chromatin remodeling,DNA repair and others.The E2F/DP transcription factors can act as either activators or repressors of transcription depending on their association to other regulatory proteins,particularly the retinoblastoma protein,or even depending to their protein structure that can define their role.In plants the E2F/DP pathway also regulates endoreduplication,a process present along the life cycle,from organ elongation to root differentiation and reproduction.These transcription factors also help plant cells to respond to environmental disturbances such as those caused by different types of radiation,or by pathogens.This review focuses on the“so called”non-canonical functions of the E2F/DP family proteins in animal and plant cells,that are in fact essential activities that connect regulatory circuits among multiple metabolic pathways by means of their atypical functions.
