cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1284429.v1
title: Gaussian Job Archive for C42H46N6O6

description: Archive of work produced using the resources of the Imperial College High Performance Computing Service.
DOI: 10.6084/m9.figshare.1284401
title: Oncogenic STRAP functions as a novel negative regulator of E-cadherin and p21<sup>Cip1</sup> by modulating the transcription factor Sp1

description: We have previously reported the identification of a novel WD-domain protein, STRAP that plays a role in maintenance of mesenchymal morphology by regulating E-cadherin and that enhances tumorigenicity partly by downregulating CDK inhibitor p21<sup>Cip1</sup>. However, the functional mechanism of regulation of E-cadherin and p21<sup>Cip1</sup> by STRAP is unknown. Here, we have employed STRAP knock out and knockdown cell models (mouse embryonic fibroblast, human cancer cell lines) to show how STRAP downregulates E-cadherin and p21<sup>Cip1</sup> by abrogating the binding of Sp1 to its consensus binding sites. Moreover, ChIP assays suggest that STRAP recruits HDAC1 to Sp1 binding sites in p21<sup>Cip1</sup> promoter. Interestingly, loss of STRAP can stabilize Sp1 by repressing its ubiquitination in G1 phase, resulting in an enhanced expression of p21<sup>Cip1</sup> by &gt;4.5-fold and cell cycle arrest. Using Bioinformatics and Microarray analyses, we have observed that 87% mouse genes downregulated by STRAP have conserved Sp1 binding sites. In NSCLC, the expression levels of STRAP inversely correlated with that of Sp1 (60%). These results suggest a novel mechanism of regulation of E-cadherin and p21<sup>Cip1</sup> by STRAP by modulating Sp1-dependent transcription, and higher expression of STRAP in lung cancer may contribute to downregulation of E-cadherin and p21<sup>Cip1</sup> and to tumor progression.
DOI: 10.6084/m9.figshare.1284400
title: Gene expression profiling of replicative and induced senescence

description: Cellular senescence is a cell cycle arrest accompanied by high expression of cyclin dependent kinase inhibitors which counteract overactive growth signals, which serves as a tumor suppressive mechanism. Senescence can be a result of telomere shortening (natural or replicative senescence) or DNA damage resulting from exogenous stressors (induced senescence). Here, we performed gene expression profiling through RNA-seq of replicative senescence, adriamycin-induced senescence, H<sub>2</sub>O<sub>2</sub>-induced senescence, and 5-aza-2-deoxycytidine-induced senescence in order to profile the pathways controlling various types of senescence. Overall, the pathways common to all 4 types of senescence were related to inflammation and the innate immune system. It was also evident that 5-aza-induced senescence mirrors natural replicative senescence due to telomere shortening. We also examined the prevalence of senescence-associated secretory phenotype (SASP) factors in the RNA-seq data, showing that it is a common characteristic of all 4 types of senescence. In addition, we could discriminate changes in gene expression due to quiescence during cellular senescence from those that were specific to senescence.
DOI: 10.6084/m9.figshare.1284397
title: Kizuna is a novel mitotic substrate for CDC25B phosphatase

description: CDC25 dual-specificity phosphatases play a central role in cell cycle control through the activation of Cyclin-Dependent Kinases (CDKs). Expression during mitosis of a stabilized CDC25B mutant (CDC25B-DDA), which cannot interact with the F-box protein βTrCP for proteasome-dependent degradation, causes mitotic defects and chromosome segregation errors in mammalian cells. We found, using the same CDC25B mutant, that stabilization and failure to degrade CDC25B during mitosis lead to the appearance of multipolar spindle cells resulting from a fragmentation of pericentriolar material (PCM) and abolish mitotic Plk1-dependent phosphorylation of Kizuna (Kiz), which is essential for the function of Kiz in maintaining spindle pole integrity. Thus, in mitosis Kiz is a new substrate of CDC25B whose dephosphorylation following CDC25B stabilization leads to the formation of multipolar spindles. Furthermore, endogenous Kiz and CDC25B interact only in mitosis, suggesting that Kiz phosphorylation depends on a balance between CDC25B and Plk1 activities. Our data identify a novel mitotic substrate of CDC25B phosphatase that plays a key role in mitosis control.
DOI: 10.6084/m9.figshare.1284401.v1
title: Oncogenic STRAP functions as a novel negative regulator of E-cadherin and p21<sup>Cip1</sup> by modulating the transcription factor Sp1

description: We have previously reported the identification of a novel WD-domain protein, STRAP that plays a role in maintenance of mesenchymal morphology by regulating E-cadherin and that enhances tumorigenicity partly by downregulating CDK inhibitor p21<sup>Cip1</sup>. However, the functional mechanism of regulation of E-cadherin and p21<sup>Cip1</sup> by STRAP is unknown. Here, we have employed STRAP knock out and knockdown cell models (mouse embryonic fibroblast, human cancer cell lines) to show how STRAP downregulates E-cadherin and p21<sup>Cip1</sup> by abrogating the binding of Sp1 to its consensus binding sites. Moreover, ChIP assays suggest that STRAP recruits HDAC1 to Sp1 binding sites in p21<sup>Cip1</sup> promoter. Interestingly, loss of STRAP can stabilize Sp1 by repressing its ubiquitination in G1 phase, resulting in an enhanced expression of p21<sup>Cip1</sup> by &gt;4.5-fold and cell cycle arrest. Using Bioinformatics and Microarray analyses, we have observed that 87% mouse genes downregulated by STRAP have conserved Sp1 binding sites. In NSCLC, the expression levels of STRAP inversely correlated with that of Sp1 (60%). These results suggest a novel mechanism of regulation of E-cadherin and p21<sup>Cip1</sup> by STRAP by modulating Sp1-dependent transcription, and higher expression of STRAP in lung cancer may contribute to downregulation of E-cadherin and p21<sup>Cip1</sup> and to tumor progression.
DOI: 10.6084/m9.figshare.1284400.v1
title: Gene expression profiling of replicative and induced senescence

description: Cellular senescence is a cell cycle arrest accompanied by high expression of cyclin dependent kinase inhibitors which counteract overactive growth signals, which serves as a tumor suppressive mechanism. Senescence can be a result of telomere shortening (natural or replicative senescence) or DNA damage resulting from exogenous stressors (induced senescence). Here, we performed gene expression profiling through RNA-seq of replicative senescence, adriamycin-induced senescence, H<sub>2</sub>O<sub>2</sub>-induced senescence, and 5-aza-2-deoxycytidine-induced senescence in order to profile the pathways controlling various types of senescence. Overall, the pathways common to all 4 types of senescence were related to inflammation and the innate immune system. It was also evident that 5-aza-induced senescence mirrors natural replicative senescence due to telomere shortening. We also examined the prevalence of senescence-associated secretory phenotype (SASP) factors in the RNA-seq data, showing that it is a common characteristic of all 4 types of senescence. In addition, we could discriminate changes in gene expression due to quiescence during cellular senescence from those that were specific to senescence.
DOI: 10.6084/m9.figshare.1284401.v2
title: Oncogenic STRAP functions as a novel negative regulator of E-cadherin and p21<sup>Cip1</sup> by modulating the transcription factor Sp1

description: We have previously reported the identification of a novel WD-domain protein, STRAP that plays a role in maintenance of mesenchymal morphology by regulating E-cadherin and that enhances tumorigenicity partly by downregulating CDK inhibitor p21<sup>Cip1</sup>. However, the functional mechanism of regulation of E-cadherin and p21<sup>Cip1</sup> by STRAP is unknown. Here, we have employed STRAP knock out and knockdown cell models (mouse embryonic fibroblast, human cancer cell lines) to show how STRAP downregulates E-cadherin and p21<sup>Cip1</sup> by abrogating the binding of Sp1 to its consensus binding sites. Moreover, ChIP assays suggest that STRAP recruits HDAC1 to Sp1 binding sites in p21<sup>Cip1</sup> promoter. Interestingly, loss of STRAP can stabilize Sp1 by repressing its ubiquitination in G1 phase, resulting in an enhanced expression of p21<sup>Cip1</sup> by &gt;4.5-fold and cell cycle arrest. Using Bioinformatics and Microarray analyses, we have observed that 87% mouse genes downregulated by STRAP have conserved Sp1 binding sites. In NSCLC, the expression levels of STRAP inversely correlated with that of Sp1 (60%). These results suggest a novel mechanism of regulation of E-cadherin and p21<sup>Cip1</sup> by STRAP by modulating Sp1-dependent transcription, and higher expression of STRAP in lung cancer may contribute to downregulation of E-cadherin and p21<sup>Cip1</sup> and to tumor progression.
DOI: 10.6084/m9.figshare.1284397.v1
title: Kizuna is a novel mitotic substrate for CDC25B phosphatase

description: CDC25 dual-specificity phosphatases play a central role in cell cycle control through the activation of Cyclin-Dependent Kinases (CDKs). Expression during mitosis of a stabilized CDC25B mutant (CDC25B-DDA), which cannot interact with the F-box protein βTrCP for proteasome-dependent degradation, causes mitotic defects and chromosome segregation errors in mammalian cells. We found, using the same CDC25B mutant, that stabilization and failure to degrade CDC25B during mitosis lead to the appearance of multipolar spindle cells resulting from a fragmentation of pericentriolar material (PCM) and abolish mitotic Plk1-dependent phosphorylation of Kizuna (Kiz), which is essential for the function of Kiz in maintaining spindle pole integrity. Thus, in mitosis Kiz is a new substrate of CDC25B whose dephosphorylation following CDC25B stabilization leads to the formation of multipolar spindles. Furthermore, endogenous Kiz and CDC25B interact only in mitosis, suggesting that Kiz phosphorylation depends on a balance between CDC25B and Plk1 activities. Our data identify a novel mitotic substrate of CDC25B phosphatase that plays a key role in mitosis control.
DOI: 10.7284/135966
title: ADCP (Acoustic Doppler Current Profiler) data collected during research cruise AT42-16 using a Hawaii UHDAS instrument system onboard the platform RV Atlantis

description: Original (unprocessed) data collected during a Field_expedition
DOI: 10.6084/m9.figshare.1284401.v4
title: Oncogenic STRAP functions as a novel negative regulator of E-cadherin and p21<sup>Cip1</sup> by modulating the transcription factor Sp1

description: We have previously reported the identification of a novel WD-domain protein, STRAP that plays a role in maintenance of mesenchymal morphology by regulating E-cadherin and that enhances tumorigenicity partly by downregulating CDK inhibitor p21<sup>Cip1</sup>. However, the functional mechanism of regulation of E-cadherin and p21<sup>Cip1</sup> by STRAP is unknown. Here, we have employed STRAP knock out and knockdown cell models (mouse embryonic fibroblast, human cancer cell lines) to show how STRAP downregulates E-cadherin and p21<sup>Cip1</sup> by abrogating the binding of Sp1 to its consensus binding sites. Moreover, ChIP assays suggest that STRAP recruits HDAC1 to Sp1 binding sites in p21<sup>Cip1</sup> promoter. Interestingly, loss of STRAP can stabilize Sp1 by repressing its ubiquitination in G1 phase, resulting in an enhanced expression of p21<sup>Cip1</sup> by &gt;4.5-fold and cell cycle arrest. Using Bioinformatics and Microarray analyses, we have observed that 87% mouse genes downregulated by STRAP have conserved Sp1 binding sites. In NSCLC, the expression levels of STRAP inversely correlated with that of Sp1 (60%). These results suggest a novel mechanism of regulation of E-cadherin and p21<sup>Cip1</sup> by STRAP by modulating Sp1-dependent transcription, and higher expression of STRAP in lung cancer may contribute to downregulation of E-cadherin and p21<sup>Cip1</sup> and to tumor progression.
DOI: 10.6084/m9.figshare.1284397.v3
title: Kizuna is a novel mitotic substrate for CDC25B phosphatase

description: CDC25 dual-specificity phosphatases play a central role in cell cycle control through the activation of Cyclin-Dependent Kinases (CDKs). Expression during mitosis of a stabilized CDC25B mutant (CDC25B-DDA), which cannot interact with the F-box protein βTrCP for proteasome-dependent degradation, causes mitotic defects and chromosome segregation errors in mammalian cells. We found, using the same CDC25B mutant, that stabilization and failure to degrade CDC25B during mitosis lead to the appearance of multipolar spindle cells resulting from a fragmentation of pericentriolar material (PCM) and abolish mitotic Plk1-dependent phosphorylation of Kizuna (Kiz), which is essential for the function of Kiz in maintaining spindle pole integrity. Thus, in mitosis Kiz is a new substrate of CDC25B whose dephosphorylation following CDC25B stabilization leads to the formation of multipolar spindles. Furthermore, endogenous Kiz and CDC25B interact only in mitosis, suggesting that Kiz phosphorylation depends on a balance between CDC25B and Plk1 activities. Our data identify a novel mitotic substrate of CDC25B phosphatase that plays a key role in mitosis control.
DOI: 10.6084/m9.figshare.1284397.v2
title: Kizuna is a novel mitotic substrate for CDC25B phosphatase

description: CDC25 dual-specificity phosphatases play a central role in cell cycle control through the activation of Cyclin-Dependent Kinases (CDKs). Expression during mitosis of a stabilized CDC25B mutant (CDC25B-DDA), which cannot interact with the F-box protein βTrCP for proteasome-dependent degradation, causes mitotic defects and chromosome segregation errors in mammalian cells. We found, using the same CDC25B mutant, that stabilization and failure to degrade CDC25B during mitosis lead to the appearance of multipolar spindle cells resulting from a fragmentation of pericentriolar material (PCM) and abolish mitotic Plk1-dependent phosphorylation of Kizuna (Kiz), which is essential for the function of Kiz in maintaining spindle pole integrity. Thus, in mitosis Kiz is a new substrate of CDC25B whose dephosphorylation following CDC25B stabilization leads to the formation of multipolar spindles. Furthermore, endogenous Kiz and CDC25B interact only in mitosis, suggesting that Kiz phosphorylation depends on a balance between CDC25B and Plk1 activities. Our data identify a novel mitotic substrate of CDC25B phosphatase that plays a key role in mitosis control.
DOI: 10.6084/m9.figshare.1284401.v3
title: Oncogenic STRAP functions as a novel negative regulator of E-cadherin and p21<sup>Cip1</sup> by modulating the transcription factor Sp1

description: We have previously reported the identification of a novel WD-domain protein, STRAP that plays a role in maintenance of mesenchymal morphology by regulating E-cadherin and that enhances tumorigenicity partly by downregulating CDK inhibitor p21<sup>Cip1</sup>. However, the functional mechanism of regulation of E-cadherin and p21<sup>Cip1</sup> by STRAP is unknown. Here, we have employed STRAP knock out and knockdown cell models (mouse embryonic fibroblast, human cancer cell lines) to show how STRAP downregulates E-cadherin and p21<sup>Cip1</sup> by abrogating the binding of Sp1 to its consensus binding sites. Moreover, ChIP assays suggest that STRAP recruits HDAC1 to Sp1 binding sites in p21<sup>Cip1</sup> promoter. Interestingly, loss of STRAP can stabilize Sp1 by repressing its ubiquitination in G1 phase, resulting in an enhanced expression of p21<sup>Cip1</sup> by &gt;4.5-fold and cell cycle arrest. Using Bioinformatics and Microarray analyses, we have observed that 87% mouse genes downregulated by STRAP have conserved Sp1 binding sites. In NSCLC, the expression levels of STRAP inversely correlated with that of Sp1 (60%). These results suggest a novel mechanism of regulation of E-cadherin and p21<sup>Cip1</sup> by STRAP by modulating Sp1-dependent transcription, and higher expression of STRAP in lung cancer may contribute to downregulation of E-cadherin and p21<sup>Cip1</sup> and to tumor progression.
DOI: 10.7284/135967
title: CTD (Conductivity, Temperature, Depth) data collected during research cruise AT42-16 using a Sea-Bird SBE-911+ instrument system onboard the platform RV Atlantis

description: Original (unprocessed) data collected during a Field_expedition
DOI: 10.6084/m9.figshare.1284400.v2
title: Gene expression profiling of replicative and induced senescence

description: Cellular senescence is a cell cycle arrest accompanied by high expression of cyclin dependent kinase inhibitors which counteract overactive growth signals, which serves as a tumor suppressive mechanism. Senescence can be a result of telomere shortening (natural or replicative senescence) or DNA damage resulting from exogenous stressors (induced senescence). Here, we performed gene expression profiling through RNA-seq of replicative senescence, adriamycin-induced senescence, H<sub>2</sub>O<sub>2</sub>-induced senescence, and 5-aza-2-deoxycytidine-induced senescence in order to profile the pathways controlling various types of senescence. Overall, the pathways common to all 4 types of senescence were related to inflammation and the innate immune system. It was also evident that 5-aza-induced senescence mirrors natural replicative senescence due to telomere shortening. We also examined the prevalence of senescence-associated secretory phenotype (SASP) factors in the RNA-seq data, showing that it is a common characteristic of all 4 types of senescence. In addition, we could discriminate changes in gene expression due to quiescence during cellular senescence from those that were specific to senescence.
DOI: 10.6084/m9.figshare.1284400.v4
title: Gene expression profiling of replicative and induced senescence

description: Cellular senescence is a cell cycle arrest accompanied by high expression of cyclin dependent kinase inhibitors which counteract overactive growth signals, which serves as a tumor suppressive mechanism. Senescence can be a result of telomere shortening (natural or replicative senescence) or DNA damage resulting from exogenous stressors (induced senescence). Here, we performed gene expression profiling through RNA-seq of replicative senescence, adriamycin-induced senescence, H<sub>2</sub>O<sub>2</sub>-induced senescence, and 5-aza-2-deoxycytidine-induced senescence in order to profile the pathways controlling various types of senescence. Overall, the pathways common to all 4 types of senescence were related to inflammation and the innate immune system. It was also evident that 5-aza-induced senescence mirrors natural replicative senescence due to telomere shortening. We also examined the prevalence of senescence-associated secretory phenotype (SASP) factors in the RNA-seq data, showing that it is a common characteristic of all 4 types of senescence. In addition, we could discriminate changes in gene expression due to quiescence during cellular senescence from those that were specific to senescence.
DOI: 10.7284/135969
title: Fluorometer data collected during research cruise AT42-16 using a WET Labs WETStar instrument system onboard the platform RV Atlantis

description: Original (unprocessed) data collected during a Field_expedition
DOI: 10.6084/m9.figshare.1284400.v3
title: Gene expression profiling of replicative and induced senescence

description: Cellular senescence is a cell cycle arrest accompanied by high expression of cyclin dependent kinase inhibitors which counteract overactive growth signals, which serves as a tumor suppressive mechanism. Senescence can be a result of telomere shortening (natural or replicative senescence) or DNA damage resulting from exogenous stressors (induced senescence). Here, we performed gene expression profiling through RNA-seq of replicative senescence, adriamycin-induced senescence, H<sub>2</sub>O<sub>2</sub>-induced senescence, and 5-aza-2-deoxycytidine-induced senescence in order to profile the pathways controlling various types of senescence. Overall, the pathways common to all 4 types of senescence were related to inflammation and the innate immune system. It was also evident that 5-aza-induced senescence mirrors natural replicative senescence due to telomere shortening. We also examined the prevalence of senescence-associated secretory phenotype (SASP) factors in the RNA-seq data, showing that it is a common characteristic of all 4 types of senescence. In addition, we could discriminate changes in gene expression due to quiescence during cellular senescence from those that were specific to senescence.
DOI: 10.6084/m9.figshare.1284396.v1
title: The E3 ligase APC/C-Cdh1 regulates MEF2A-dependent transcription by targeting SUMO-specific protease 2 for ubiquitination and degradation

description: Activity-dependent stimuli induced a calcineurin-mediated dephosphorylation of the transcriptional factor MEF2A at serine408 and promoted a switch from SUMOylation to acetylation at lysine403 which led to MEF2A transcriptional activation. We previously identified SENP2 is the de-SUMOylation enzyme for MEF2A and promotes MEF2A-dependent transcription. We report here a requirement for APC<sup>Cdh1</sup>-SENP2-MEF2A axis in the regulation of MEF2A transcriptional activation. APC<sup>Cdh1</sup> interacts with and targets SENP2 for ubiquitination and destruction in the cytoplasm by recognizing a conserved canonical D-box motif in SENP2. Moreover, Cdh1 regulates the transcriptional activity of MEF2A in a SENP2 dependent manner. Activity-dependent stimuli prevented APC<sup>Cdh1</sup>-induced SENP2 ubiquitination, promoted SENP2 nuclear accumulations, and caused MEF2A de-SUMOylation and MEF2A acetylation, leading to MEF2A transcriptional activation. Thus, our findings defined a post-transcriptional mechanism underlying activity-dependent stimuli-induced MEF2A transcriptional activation.
DOI: 10.6084/m9.figshare.1284396.v3
title: The E3 ligase APC/C-Cdh1 regulates MEF2A-dependent transcription by targeting SUMO-specific protease 2 for ubiquitination and degradation

description: Activity-dependent stimuli induced a calcineurin-mediated dephosphorylation of the transcriptional factor MEF2A at serine408 and promoted a switch from SUMOylation to acetylation at lysine403 which led to MEF2A transcriptional activation. We previously identified SENP2 is the de-SUMOylation enzyme for MEF2A and promotes MEF2A-dependent transcription. We report here a requirement for APC<sup>Cdh1</sup>-SENP2-MEF2A axis in the regulation of MEF2A transcriptional activation. APC<sup>Cdh1</sup> interacts with and targets SENP2 for ubiquitination and destruction in the cytoplasm by recognizing a conserved canonical D-box motif in SENP2. Moreover, Cdh1 regulates the transcriptional activity of MEF2A in a SENP2 dependent manner. Activity-dependent stimuli prevented APC<sup>Cdh1</sup>-induced SENP2 ubiquitination, promoted SENP2 nuclear accumulations, and caused MEF2A de-SUMOylation and MEF2A acetylation, leading to MEF2A transcriptional activation. Thus, our findings defined a post-transcriptional mechanism underlying activity-dependent stimuli-induced MEF2A transcriptional activation.
DOI: 10.7284/135962
title: GNSS (Global Navigation Satellite System) data collected during research cruise AT42-16 using a C&C C-Nav 3050 instrument system onboard the platform RV Atlantis

description: Original (unprocessed) data collected during a Field_expedition