Differential protein-protein interactions underlie signaling mediated by the TCR and a 4-1BB domain-containing CAR
Sci Signal. 2024 Mar 5;17(826):eadd4671. doi: 10.1126/scisignal.add4671. Epub 2024 Mar 5.ABSTRACTCells rely on activity-dependent protein-protein interactions to convey biological signals. For chimeric antigen receptor (CAR) T cells containing a 4-1BB costimulatory domain, receptor engagement is thought to stimulate the formation of protein complexes similar to those stimulated by T cell receptor (TCR)-mediated signaling, but the number and type of protein interaction-mediating binding domains differ between CARs and TCRs. Here, we performed coimmunoprecipitation mass spectrometry analysis of a second-generation, CD19-dire...
Source: Science Signaling - March 5, 2024 Category: Biomedical Science Authors: Samuel A Ritmeester-Loy Isabella H Draper Eric C Bueter Jonathan D Lautz Yue Zhang-Wong Joshua A Gustafson Ashley L Wilson Chenwei Lin Philip R Gafken Michael C Jensen Rimas Orentas Stephen E P Smith Source Type: research
eEF1A2 promotes PTEN-GSK3 β-SCF complex-dependent degradation of Aurora kinase A and is inactivated in breast cancer
Sci Signal. 2024 Mar 5;17(826):eadh4475. doi: 10.1126/scisignal.adh4475. Epub 2024 Mar 5.ABSTRACTThe translation elongation factor eEF1A promotes protein synthesis. Its methylation by METTL13 increases its activity, supporting tumor growth. However, in some cancers, a high abundance of eEF1A isoforms is associated with a good prognosis. Here, we found that eEF1A2 exhibited oncogenic or tumor-suppressor functions depending on its interaction with METTL13 or the phosphatase PTEN, respectively. METTL13 and PTEN competed for interaction with eEF1A2 in the same structural domain. PTEN-bound eEF1A2 promoted the ubiquitination an...
Source: Science Signaling - March 5, 2024 Category: Biomedical Science Authors: Warapen Treekitkarnmongkol Luisa M Solis Deivendran Sankaran Mihai Gagea Pankaj K Singh Ragini Mistry Tristian Nguyen Kazuharu Kai Jiajun Liu Kaori Sasai Yoshimi Jitsumori Jianwen Liu Norio Nagao Fabio Stossi Michael A Mancini Ignacio I Wistuba Alastair M Source Type: research
Bring in the B team
Sci Signal. 2024 Mar 5;17(826):eado9536. doi: 10.1126/scisignal.ado9536. Epub 2024 Mar 5.ABSTRACTATP released by osteoblasts signals through the purinergic receptor P2RX4 to optimize plasma cell survival.PMID:38442202 | DOI:10.1126/scisignal.ado9536 (Source: Science Signaling)
Source: Science Signaling - March 5, 2024 Category: Biomedical Science Authors: Amy E Baek Source Type: research
A way to block TBK1 in ccRCC
Sci Signal. 2024 Feb 27;17(825):eado8046. doi: 10.1126/scisignal.ado8046. Epub 2024 Feb 27.ABSTRACTTargeting a driver of TBK1 kinase activity may slow the growth of kidney tumors.PMID:38412253 | DOI:10.1126/scisignal.ado8046 (Source: Science Signaling)
Source: Science Signaling - February 27, 2024 Category: Biomedical Science Authors: Leslie K Ferrarelli Source Type: research
ALOX5 drives the pyroptosis of CD4 < sup > + < /sup > T cells and tissue inflammation in rheumatoid arthritis
Sci Signal. 2024 Feb 27;17(825):eadh1178. doi: 10.1126/scisignal.adh1178. Epub 2024 Feb 27.ABSTRACTPyroptosis, an inflammatory form of programmed cell death, is linked to the pathology of rheumatoid arthritis (RA). Here, we investigated the molecular mechanism underlying pyroptosis in T cells isolated from patients with RA. Compared with healthy individuals, patients with RA had more pyroptotic CD4+ T cells in blood and synovia, which correlated with clinical measures of disease activity. Moreover, the mRNA expression and protein abundance of arachidonate 5-lipoxygenase (ALOX5), which converts arachidonic acid to leukotrie...
Source: Science Signaling - February 27, 2024 Category: Biomedical Science Authors: Hao Cai Jianhua Zhang Hua Xu Weiwei Sun Weijie Wu Chen Dong Ping Zhou Chengbin Xue Yunyi Nan Yingchen Ni Xinyuan Wu Zhifeng Gu Minhao Chen Youhua Wang Source Type: research
Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation
Sci Signal. 2024 Feb 27;17(825):eadf2670. doi: 10.1126/scisignal.adf2670. Epub 2024 Feb 27.ABSTRACTMore than 50% of human tumors display hyperactivation of the serine/threonine kinase AKT. Despite evidence of clinical efficacy, the therapeutic window of the current generation of AKT inhibitors could be improved. Here, we report the development of a second-generation AKT degrader, INY-05-040, which outperformed catalytic AKT inhibition with respect to cellular suppression of AKT-dependent phenotypes in breast cancer cell lines. A growth inhibition screen with 288 cancer cell lines confirmed that INY-05-040 had a substantial...
Source: Science Signaling - February 27, 2024 Category: Biomedical Science Authors: Emily C Erickson Inchul You Grace Perry Aurelien Dugourd Katherine A Donovan Claire Crafter Jeffrey W Johannes Stuart Williamson Jennifer I Moss Susana Ros Robert E Ziegler Simon T Barry Eric S Fischer Nathanael S Gray Ralitsa R Madsen Alex Toker Source Type: research
A way to block TBK1 in ccRCC
Sci Signal. 2024 Feb 27;17(825):eado8046. doi: 10.1126/scisignal.ado8046. Epub 2024 Feb 27.ABSTRACTTargeting a driver of TBK1 kinase activity may slow the growth of kidney tumors.PMID:38412253 | DOI:10.1126/scisignal.ado8046 (Source: Science Signaling)
Source: Science Signaling - February 27, 2024 Category: Biomedical Science Authors: Leslie K Ferrarelli Source Type: research
ALOX5 drives the pyroptosis of CD4 < sup > + < /sup > T cells and tissue inflammation in rheumatoid arthritis
Sci Signal. 2024 Feb 27;17(825):eadh1178. doi: 10.1126/scisignal.adh1178. Epub 2024 Feb 27.ABSTRACTPyroptosis, an inflammatory form of programmed cell death, is linked to the pathology of rheumatoid arthritis (RA). Here, we investigated the molecular mechanism underlying pyroptosis in T cells isolated from patients with RA. Compared with healthy individuals, patients with RA had more pyroptotic CD4+ T cells in blood and synovia, which correlated with clinical measures of disease activity. Moreover, the mRNA expression and protein abundance of arachidonate 5-lipoxygenase (ALOX5), which converts arachidonic acid to leukotrie...
Source: Science Signaling - February 27, 2024 Category: Biomedical Science Authors: Hao Cai Jianhua Zhang Hua Xu Weiwei Sun Weijie Wu Chen Dong Ping Zhou Chengbin Xue Yunyi Nan Yingchen Ni Xinyuan Wu Zhifeng Gu Minhao Chen Youhua Wang Source Type: research
Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation
Sci Signal. 2024 Feb 27;17(825):eadf2670. doi: 10.1126/scisignal.adf2670. Epub 2024 Feb 27.ABSTRACTMore than 50% of human tumors display hyperactivation of the serine/threonine kinase AKT. Despite evidence of clinical efficacy, the therapeutic window of the current generation of AKT inhibitors could be improved. Here, we report the development of a second-generation AKT degrader, INY-05-040, which outperformed catalytic AKT inhibition with respect to cellular suppression of AKT-dependent phenotypes in breast cancer cell lines. A growth inhibition screen with 288 cancer cell lines confirmed that INY-05-040 had a substantial...
Source: Science Signaling - February 27, 2024 Category: Biomedical Science Authors: Emily C Erickson Inchul You Grace Perry Aurelien Dugourd Katherine A Donovan Claire Crafter Jeffrey W Johannes Stuart Williamson Jennifer I Moss Susana Ros Robert E Ziegler Simon T Barry Eric S Fischer Nathanael S Gray Ralitsa R Madsen Alex Toker Source Type: research
A way to block TBK1 in ccRCC
Sci Signal. 2024 Feb 27;17(825):eado8046. doi: 10.1126/scisignal.ado8046. Epub 2024 Feb 27.ABSTRACTTargeting a driver of TBK1 kinase activity may slow the growth of kidney tumors.PMID:38412253 | DOI:10.1126/scisignal.ado8046 (Source: Science Signaling)
Source: Science Signaling - February 27, 2024 Category: Biomedical Science Authors: Leslie K Ferrarelli Source Type: research
ALOX5 drives the pyroptosis of CD4 < sup > + < /sup > T cells and tissue inflammation in rheumatoid arthritis
Sci Signal. 2024 Feb 27;17(825):eadh1178. doi: 10.1126/scisignal.adh1178. Epub 2024 Feb 27.ABSTRACTPyroptosis, an inflammatory form of programmed cell death, is linked to the pathology of rheumatoid arthritis (RA). Here, we investigated the molecular mechanism underlying pyroptosis in T cells isolated from patients with RA. Compared with healthy individuals, patients with RA had more pyroptotic CD4+ T cells in blood and synovia, which correlated with clinical measures of disease activity. Moreover, the mRNA expression and protein abundance of arachidonate 5-lipoxygenase (ALOX5), which converts arachidonic acid to leukotrie...
Source: Science Signaling - February 27, 2024 Category: Biomedical Science Authors: Hao Cai Jianhua Zhang Hua Xu Weiwei Sun Weijie Wu Chen Dong Ping Zhou Chengbin Xue Yunyi Nan Yingchen Ni Xinyuan Wu Zhifeng Gu Minhao Chen Youhua Wang Source Type: research
Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation
Sci Signal. 2024 Feb 27;17(825):eadf2670. doi: 10.1126/scisignal.adf2670. Epub 2024 Feb 27.ABSTRACTMore than 50% of human tumors display hyperactivation of the serine/threonine kinase AKT. Despite evidence of clinical efficacy, the therapeutic window of the current generation of AKT inhibitors could be improved. Here, we report the development of a second-generation AKT degrader, INY-05-040, which outperformed catalytic AKT inhibition with respect to cellular suppression of AKT-dependent phenotypes in breast cancer cell lines. A growth inhibition screen with 288 cancer cell lines confirmed that INY-05-040 had a substantial...
Source: Science Signaling - February 27, 2024 Category: Biomedical Science Authors: Emily C Erickson Inchul You Grace Perry Aurelien Dugourd Katherine A Donovan Claire Crafter Jeffrey W Johannes Stuart Williamson Jennifer I Moss Susana Ros Robert E Ziegler Simon T Barry Eric S Fischer Nathanael S Gray Ralitsa R Madsen Alex Toker Source Type: research
A way to block TBK1 in ccRCC
Sci Signal. 2024 Feb 27;17(825):eado8046. doi: 10.1126/scisignal.ado8046. Epub 2024 Feb 27.ABSTRACTTargeting a driver of TBK1 kinase activity may slow the growth of kidney tumors.PMID:38412253 | DOI:10.1126/scisignal.ado8046 (Source: Science Signaling)
Source: Science Signaling - February 27, 2024 Category: Biomedical Science Authors: Leslie K Ferrarelli Source Type: research
ALOX5 drives the pyroptosis of CD4 < sup > + < /sup > T cells and tissue inflammation in rheumatoid arthritis
Sci Signal. 2024 Feb 27;17(825):eadh1178. doi: 10.1126/scisignal.adh1178. Epub 2024 Feb 27.ABSTRACTPyroptosis, an inflammatory form of programmed cell death, is linked to the pathology of rheumatoid arthritis (RA). Here, we investigated the molecular mechanism underlying pyroptosis in T cells isolated from patients with RA. Compared with healthy individuals, patients with RA had more pyroptotic CD4+ T cells in blood and synovia, which correlated with clinical measures of disease activity. Moreover, the mRNA expression and protein abundance of arachidonate 5-lipoxygenase (ALOX5), which converts arachidonic acid to leukotrie...
Source: Science Signaling - February 27, 2024 Category: Biomedical Science Authors: Hao Cai Jianhua Zhang Hua Xu Weiwei Sun Weijie Wu Chen Dong Ping Zhou Chengbin Xue Yunyi Nan Yingchen Ni Xinyuan Wu Zhifeng Gu Minhao Chen Youhua Wang Source Type: research
Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation
Sci Signal. 2024 Feb 27;17(825):eadf2670. doi: 10.1126/scisignal.adf2670. Epub 2024 Feb 27.ABSTRACTMore than 50% of human tumors display hyperactivation of the serine/threonine kinase AKT. Despite evidence of clinical efficacy, the therapeutic window of the current generation of AKT inhibitors could be improved. Here, we report the development of a second-generation AKT degrader, INY-05-040, which outperformed catalytic AKT inhibition with respect to cellular suppression of AKT-dependent phenotypes in breast cancer cell lines. A growth inhibition screen with 288 cancer cell lines confirmed that INY-05-040 had a substantial...
Source: Science Signaling - February 27, 2024 Category: Biomedical Science Authors: Emily C Erickson Inchul You Grace Perry Aurelien Dugourd Katherine A Donovan Claire Crafter Jeffrey W Johannes Stuart Williamson Jennifer I Moss Susana Ros Robert E Ziegler Simon T Barry Eric S Fischer Nathanael S Gray Ralitsa R Madsen Alex Toker Source Type: research
