Pub Date : 2021-05-05eCollection Date: 2021-01-01DOI: 10.1080/23723556.2021.1896348
Xin Zhou, Yanghao Zhong, Jin Zhang
mTORC1 integrates diverse upstream signals to control cell growth and metabolism. We previously showed that mTORC1 activity is spatially compartmentalized to ensure its signaling specificity. In a recently published study, we demonstrated the existence of mTORC1 activity in the nucleus and identified a unique mode of its regulation in the nuclear compartment.
{"title":"Regulation of nuclear mTORC1.","authors":"Xin Zhou, Yanghao Zhong, Jin Zhang","doi":"10.1080/23723556.2021.1896348","DOIUrl":"https://doi.org/10.1080/23723556.2021.1896348","url":null,"abstract":"<p><p>mTORC1 integrates diverse upstream signals to control cell growth and metabolism. We previously showed that mTORC1 activity is spatially compartmentalized to ensure its signaling specificity. In a recently published study, we demonstrated the existence of mTORC1 activity in the nucleus and identified a unique mode of its regulation in the nuclear compartment.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23723556.2021.1896348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39010559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-05eCollection Date: 2021-01-01DOI: 10.1080/23723556.2021.1915076
Yu-Hsuan Chen, Ruey-Hwa Chen
Ubiquitin-proteasome system and autophagy are the two major recycling processes. Our recent work uncovers a K29/K48 branched ubiquitination on the phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3, best known as VPS34). This ubiquitination is positively or negatively regulated under pathophysiological conditions to influence on autophagy, proteostasis and lipid homeostasis.
{"title":"Regulation of autophagy by VPS34 branched ubiquitination controls proteostasis and liver metabolism.","authors":"Yu-Hsuan Chen, Ruey-Hwa Chen","doi":"10.1080/23723556.2021.1915076","DOIUrl":"https://doi.org/10.1080/23723556.2021.1915076","url":null,"abstract":"<p><p>Ubiquitin-proteasome system and autophagy are the two major recycling processes. Our recent work uncovers a K29/K48 branched ubiquitination on the phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3, best known as VPS34). This ubiquitination is positively or negatively regulated under pathophysiological conditions to influence on autophagy, proteostasis and lipid homeostasis.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23723556.2021.1915076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39012049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-05eCollection Date: 2021-01-01DOI: 10.1080/23723556.2021.1891831
Amaia Arruabarrena-Aristorena, Eneda Toska
ABSTRACT Forkhead box protein A1 (FOXA1) is a pioneer transcription factor that contributes to chromatin opening to allow binding of estrogen receptor (ER) in ER+ breast cancer. Mutations in FOXA1 are recurrent in breast cancer but the functional consequences of these mutations remain unknown. We identified that FOXA1 mutations are associated with worse outcomes to endocrine therapy by inducing alternative chromatin profiles and gene activity in breast cancer.
{"title":"<i>FOXA1</i> mutations influence the therapeutic response of breast cancer by altering chromatin state.","authors":"Amaia Arruabarrena-Aristorena, Eneda Toska","doi":"10.1080/23723556.2021.1891831","DOIUrl":"https://doi.org/10.1080/23723556.2021.1891831","url":null,"abstract":"ABSTRACT Forkhead box protein A1 (FOXA1) is a pioneer transcription factor that contributes to chromatin opening to allow binding of estrogen receptor (ER) in ER+ breast cancer. Mutations in FOXA1 are recurrent in breast cancer but the functional consequences of these mutations remain unknown. We identified that FOXA1 mutations are associated with worse outcomes to endocrine therapy by inducing alternative chromatin profiles and gene activity in breast cancer.","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23723556.2021.1891831","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39010557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-03eCollection Date: 2021-01-01DOI: 10.1080/23723556.2021.1911290
Gerard Duart, Ismael Mingarro, Luis Martinez-Gil
Viral control of apoptosis occurs through the expression of viral encoded anti-apoptotic B-cell lymphoma 2 (BCL2) analogs. These proteins are thought to restrain apoptosis by interacting with cellular BCL2 family members. We identified that protein-protein interactions between cellular and viral BCL2 transmembrane domains are crucial for the viral protein's function.
{"title":"The importance of transmembrane domain interactions in the viral control of apoptosis.","authors":"Gerard Duart, Ismael Mingarro, Luis Martinez-Gil","doi":"10.1080/23723556.2021.1911290","DOIUrl":"https://doi.org/10.1080/23723556.2021.1911290","url":null,"abstract":"<p><p>Viral control of apoptosis occurs through the expression of viral encoded anti-apoptotic B-cell lymphoma 2 (BCL2) analogs. These proteins are thought to restrain apoptosis by interacting with cellular BCL2 family members. We identified that protein-protein interactions between cellular and viral BCL2 transmembrane domains are crucial for the viral protein's function.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23723556.2021.1911290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39012046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-29eCollection Date: 2021-01-01DOI: 10.1080/23723556.2021.1898523
Kathryn T Bieging-Rolett, Laura D Attardi
The tumor protein p53 (TP53, best known as p53) transcription factor is a critical tumor suppressor, but those p53-inducible genes most important for tumor suppression have remained unclear. Using unbiased RNA interference and CRISPR (Clustered Regularly Interspersed Palindromic Repeats)/Cas9 (CRISPR-associated protein 9) screens, genetically engineered mouse models, human cancer genome analysis, and integrative eCLIP-sequencing and RNA-sequencing analyses, we reveal a new branch of p53-mediated tumor suppression involving the RNA splicing regulator Zinc finger Matrin-type 3, Zmat3.
{"title":"Zmat3 splices together p53-dependent tumor suppression.","authors":"Kathryn T Bieging-Rolett, Laura D Attardi","doi":"10.1080/23723556.2021.1898523","DOIUrl":"https://doi.org/10.1080/23723556.2021.1898523","url":null,"abstract":"<p><p>The tumor protein p53 (TP53, best known as p53) transcription factor is a critical tumor suppressor, but those p53-inducible genes most important for tumor suppression have remained unclear. Using unbiased RNA interference and CRISPR (Clustered Regularly Interspersed Palindromic Repeats)/Cas9 (CRISPR-associated protein 9) screens, genetically engineered mouse models, human cancer genome analysis, and integrative eCLIP-sequencing and RNA-sequencing analyses, we reveal a new branch of p53-mediated tumor suppression involving the RNA splicing regulator Zinc finger Matrin-type 3, Zmat3.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23723556.2021.1898523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39010561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-27eCollection Date: 2021-01-01DOI: 10.1080/23723556.2021.1919006
Yuelong Yan, Guang Lei, Boyi Gan
Ferroptosis is a cell death mechanism triggered by lipid peroxidation. Our recent study linked cyst(e)ine availability with glutathione peroxidase 4 (GPX4) protein synthesis and ferroptosis mitigation via a Rag-mechanistic target of rapamycin complex 1 (mTORC1) axis, and proposed that co-targeting mTORC1 and ferroptosis is a promising strategy for cancer therapy.
{"title":"A mTORC1-mediated cyst(e)ine sensing mechanism governing GPX4 synthesis and ferroptosis.","authors":"Yuelong Yan, Guang Lei, Boyi Gan","doi":"10.1080/23723556.2021.1919006","DOIUrl":"https://doi.org/10.1080/23723556.2021.1919006","url":null,"abstract":"<p><p>Ferroptosis is a cell death mechanism triggered by lipid peroxidation. Our recent study linked cyst(e)ine availability with glutathione peroxidase 4 (GPX4) protein synthesis and ferroptosis mitigation via a Rag-mechanistic target of rapamycin complex 1 (mTORC1) axis, and proposed that co-targeting mTORC1 and ferroptosis is a promising strategy for cancer therapy.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23723556.2021.1919006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39012050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-25DOI: 10.1080/23723556.2021.1914291
Christina Cooley, Le Su
The function of histone deacetylase 2 (HDAC2) in transcriptional regulation and its role in oncogenesis have been well established. Here we discuss a transcription-independent HDAC2 pathway controlling cancer-related protein stability via the mouse double minute 2 homolog (MDM2) ubiquitin ligase. In synovial sarcoma, HDAC2 inactivation demonstrates significant therapeutic effect by degradation of the SS18-SSX driver oncoprotein.
{"title":"HDAC2 links ubiquitination to tumor suppression in synovial sarcoma.","authors":"Christina Cooley, Le Su","doi":"10.1080/23723556.2021.1914291","DOIUrl":"https://doi.org/10.1080/23723556.2021.1914291","url":null,"abstract":"<p><p>The function of histone deacetylase 2 (HDAC2) in transcriptional regulation and its role in oncogenesis have been well established. Here we discuss a transcription-independent HDAC2 pathway controlling cancer-related protein stability via the mouse double minute 2 homolog (MDM2) ubiquitin ligase. In synovial sarcoma, HDAC2 inactivation demonstrates significant therapeutic effect by degradation of the SS18-SSX driver oncoprotein.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23723556.2021.1914291","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39012047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-25eCollection Date: 2021-01-01DOI: 10.1080/23723556.2021.1915075
Yael Cohen-Sharir, Uri Ben-David
Aneuploidy, a common feature of cancer cells, results in increased sensitivity to the inhibition of the spindle assembly checkpoint (SAC) and the mitotic motor protein Kinesin Family Member 18A (KIF18A). We discuss the importance of drugs targeting SAC core members and KIF18A. We stress the need to assess the sensitivity to this class of drugs at appropriate time points, and propose that aneuploidy could serve as a biomarker to stratify patients for SAC-targeting treatments.
{"title":"Relevance of aneuploidy for cancer therapies targeting the spindle assembly checkpoint and KIF18A.","authors":"Yael Cohen-Sharir, Uri Ben-David","doi":"10.1080/23723556.2021.1915075","DOIUrl":"https://doi.org/10.1080/23723556.2021.1915075","url":null,"abstract":"<p><p>Aneuploidy, a common feature of cancer cells, results in increased sensitivity to the inhibition of the spindle assembly checkpoint (SAC) and the mitotic motor protein Kinesin Family Member 18A (KIF18A). We discuss the importance of drugs targeting SAC core members and KIF18A. We stress the need to assess the sensitivity to this class of drugs at appropriate time points, and propose that aneuploidy could serve as a biomarker to stratify patients for SAC-targeting treatments.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23723556.2021.1915075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39012048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-22eCollection Date: 2021-01-01DOI: 10.1080/23723556.2021.1905489
Marina Farkas, Steven McMahon
For recognition of specific regulatory sequences in the genome (i.e., response elements, REs), the tumor suppressor protein 53 kDa (p53) exhibits dose-dependent selectivity. In general, binding to REs linked to target genes involved in the positive regulation of cell death requires higher levels of p53 than those connected to cell survival. Our recent findings provide a mechanistic explanation for this phenomenon. Specifically, we demonstrate that subtle differences in DNA shape, encoded in RE DNA sequence, determine the utilization of two biochemically distinct DNA-binding modes, ultimately connected to different biological outcomes.
{"title":"Unlocking p53 response elements: DNA shape is the key.","authors":"Marina Farkas, Steven McMahon","doi":"10.1080/23723556.2021.1905489","DOIUrl":"https://doi.org/10.1080/23723556.2021.1905489","url":null,"abstract":"<p><p>For recognition of specific regulatory sequences in the genome (i.e., response elements, REs), the tumor suppressor protein 53 kDa (p53) exhibits dose-dependent selectivity. In general, binding to REs linked to target genes involved in the positive regulation of cell death requires higher levels of p53 than those connected to cell survival. Our recent findings provide a mechanistic explanation for this phenomenon. Specifically, we demonstrate that subtle differences in DNA shape, encoded in RE DNA sequence, determine the utilization of two biochemically distinct DNA-binding modes, ultimately connected to different biological outcomes.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23723556.2021.1905489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39010565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-18DOI: 10.1080/23723556.2021.1910008
Helga B Landsverk, Lise E Sandquist, Lilli T E Bay, Randi G Syljuåsen
Conflicts between transcription and replication are a major source of replication stress. Our recent findings show that proper dephosphorylation of Serine 5 in the carboxy-terminal domain (CTD) of DNA-directed RNA polymerase II subunit RPB1 is needed to prevent such conflicts in human cells.
{"title":"New link between the RNA polymerase II-CTD and replication stress.","authors":"Helga B Landsverk, Lise E Sandquist, Lilli T E Bay, Randi G Syljuåsen","doi":"10.1080/23723556.2021.1910008","DOIUrl":"https://doi.org/10.1080/23723556.2021.1910008","url":null,"abstract":"<p><p>Conflicts between transcription and replication are a major source of replication stress. Our recent findings show that proper dephosphorylation of Serine 5 in the carboxy-terminal domain (CTD) of DNA-directed RNA polymerase II subunit RPB1 is needed to prevent such conflicts in human cells.</p>","PeriodicalId":37292,"journal":{"name":"Molecular and Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2021-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23723556.2021.1910008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39010566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}