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NSD2 binds PSMD14. 49 / 49
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"Cell Counting Kit (CCK) assays indicated that depletion of PSMD14, NSD2, or RELA inhibited cell proliferation, whereas PSMD14 overexpression promoted the proliferation of LP-1 cells, an effect that wa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Considering NSD2’s role as an H3K36me2 methyltransferase 4 and our observation of PSMD14’s interaction with NSD2 on chromatin, we postulate that PSMD14 might be also functionally linked to epigenetic [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Furthermore, we intersected these with the CUT&Tag data of PSMD14-NSD2 complex, and a total of 1,092 overlapped genes were identified ( Figure S3 B)."
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"Exploring the PSMD14-NSD2 complex in diverse physiological and pathological contexts is also crucial for understanding of its multifaceted functions in cell fate determination and therapeutic potentia[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
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"To investigate the genome-wide transcription targets of PSMD14-NSD2 complex and to explore the gain of function of PSMD14-NSD2 complex in MM, cleavage under targets and tagmentation (CUT&Tag) was perf[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
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"The PSMD14 data were then cross-analyzed with NSD2 data for overlapping sequences, which were then analyzed by gene ontology for targets with a corresponding promoter region spanning ≤ 3 kb of the tra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"A total of 2,907 PSMD14-NSD2 complex target genes were identified, which were then assigned to various cellular biological processes using DAVID (the Database for Annotation, Visualization and Integra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
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"A total of 2,907 PSMD14-NSD2 complex target genes were identified, which were then assigned to various cellular biological processes using DAVID (the Database for Annotation, Visualization and Integra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Strikingly, among the signaling pathways that are epigenetically regulated by PSMD14-NSD2 complex, IκB kinase/nuclear factor κB (NF-κB) signaling pathways and cell cycle (represented by RELA and SMAD3[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The co-immunoprecipitation assay with nuclear extracts still detected the interaction between PSMD14 and NSD2 upon co-depletion of PSMD1 and PSMD2 ( Figure S1 C), suggesting that the physical interact[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
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"Co-immunoprecipitation assays in chromatin-bound fractions of LP-1 cells and glutathione S-transferase (GST) pull-down assays showed that DNase I treatment disrupted the interaction between PSMD14 and[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Together, these results support a notion that PSMD14 promotes myeloma cell proliferation and colony formation and represses myeloma cell apoptosis, and that it does so through transcription activation[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"It seems plausible that the aberrant expression of NSD2 and/or PSMD14 can promote a gain of function of PSMD14-NSD2 complex in the nucleus that unleashes an oncogenic epigenetic reprogramming to drive[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"These observations indicate that the interaction of PSMD14 with NSD2 on chromatin is required for functional coordination between PSMD14-catalyzed H2AK119 deubiquitination and NSD2-directed H3K36me2 d[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"First, while we have presented the biochemical evidence of the mutual exclusion of H2AK119ub removal with H3K36me2 deposition in gene transcription, we have not explored whether NSD2’s PHD1–3 domain i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
sparser
"Strikingly, among the signaling pathways that are epigenetically regulated by PSMD14-NSD2 complex, IκB kinase/nuclear factor κB (NF-κB) signaling pathways and cell cycle (represented by RELA and SMAD3[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"To further investigate the PSMD14-NSD2 complex track with H2AK119ub or H3K36me2, CUT&Tag was performed in LP-1 cells infected with lentiviruses carrying control shRNA or PSMD14 shRNA using antibodies [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
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"Furthermore, we intersected these with the CUT&Tag data of PSMD14-NSD2 complex, and a total of 1,092 overlapped genes were identified ( Figure S3 B)."
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"14 To understand the impact of inhibiting of PSMD14 beyond the proteasome, we profiled the PSMD14 interactome and found that PSMD14 is physically associated with the myeloma driver NSD2 on chromatin [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"However, the elution pattern of native PSMD14 overlapped with that of NSD2 in chromatin-bound fraction, but not with the four other examined proteasome subunits ( Figure 1 H), supporting that the asso[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Collectively, these observations support that PSMD14 and NSD2 functionally coordinate in the epigenetic regulation of H2AK119 deubiquitination and H3K36me2 deposition, independent of the 19 S RP.To su[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
reach
"To investigate the genome-wide transcription targets of PSMD14-NSD2 complex and to explore the gain of function of PSMD14-NSD2 complex in MM, cleavage under targets and tagmentation (CUT&Tag) was perf[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
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"A recent study of myelomagenesis reported that NSD2 interacts with the proteasome component PSMD14 on chromatin and that NSD2-directed H3K36me2 and PSMD14-catalyzed H2AK119 deubiquitination are functionally coordinated during the transcriptional activation of target genes linked to NF-κB (IκB kinase/nuclear factor κB) signaling ( xref C) ( xref )."
38371593
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"We observed that PSMD14 knockdown led to elevated H2AK119ub enrichment and reduced H3K36me2 enrichment at the promoters of PSMD14-NSD2 complex target genes including RELA , SMAD3 , MEN1 , and PLK1 ( F[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"To validate the CUT&Tag results of target genes by PSMD14-NSD2 complex, we performed quantitative chromatin immunoprecipitation (ChIP) (qChIP) analysis, confirming the specific occupancy of PSMD14 and[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Strikingly, RELA, a product of the gene that was identified by CUT&Tag to be targeted by the PSMD14-NSD2 complex, is among the list ( Figures 4 A and S4 A)."
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"18 To verify that PSMD14-NSD2 interaction occurs in vivo , co-immunoprecipitation experiments were conducted."
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"These results suggest that PSMD14 indeed binds to chromatin and interacts with full-length NSD2 on chromatin in a likely functionally relevant manner.To investigate whether the interaction between PSM[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
reach
"The PSMD14 data were then cross-analyzed with NSD2 data for overlapping sequences, which were then analyzed by gene ontology for targets with a corresponding promoter region spanning ≤ 3 kb of the tra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
reach
"We observed that PSMD14 knockdown led to elevated H2AK119ub enrichment and reduced H3K36me2 enrichment at the promoters of PSMD14-NSD2 complex target genes including RELA , SMAD3 , MEN1 , and PLK1 ( F[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"We detected discrete spots in the nucleus, supporting that PSMD14 interacts with NSD2 in the nucleus ( Figures 1 D and S1 B)."
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"These results strongly support that PSMD14-catalyzed H2AK119 deubiquitination and NSD2-directed H3K36 dimethylation are functionally coordinated in transcriptional activation of target genes linked to[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
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"These observations are consistent with the physical association and functional coordination between PSMD14 and NSD2 as well as with transcription activation of RELA by PSMD14-NSD2 complex, supporting [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
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"Given that NSD2 is a driver for myelomagenesis 8 and considering our observations that PSMD14 and NSD2 are physically associated and functionally coordinated, it is reasonable to believe that PSMD14 a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
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"We further examined the PSMD14-NSD2 interaction by performing cell fractionation with detergent to separate the cytoplasmic, soluble nuclear, and chromatin-bound (insoluble nuclear) fractions of LP-1 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
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"Strikingly, RELA, a product of the gene that was identified by CUT&Tag to be targeted by the PSMD14-NSD2 complex, is among the list ( Figures 4 A and S4 A)."
37935198
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"To investigate whether the interaction between PSMD14 and NSD2 is in the context of the 19 S RP, we disrupted the 19 S RP by knocking down PSMD1 and PSMD2, the scaffold components of the 19 S RP, 20 i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"For example, the proteasome component PSMD14, a novel histone H2AK119 deubiquitinase, interacts with the histone H3K36 dimethyl transferase NSD2 at chromatin and facilitates H3K36 dimethyl initiation."
39660050
sparser
"Cell Counting Kit (CCK) assays indicated that depletion of PSMD14, NSD2, or RELA inhibited cell proliferation, whereas PSMD14 overexpression promoted the proliferation of LP-1 cells, an effect that wa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
sparser
"Given that PSMD14 interacts with NSD2 on chromatin, we wondered if the interaction between PSMD14 and NSD2 is dependent on DNA."
37935198
sparser
"Co-immunoprecipitation assays in chromatin-bound fractions of LP-1 cells and glutathione S-transferase (GST) pull-down assays showed that DNase I treatment disrupted the interaction between PSMD14 and[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
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"The results showed that NSD2 N , NSD2 ΔPHD1–3 , and NSD2 ΔPHD1 did not bind to PSMD14 ( Figure 1 G), suggesting that NSD2’s PHD1 domain is responsible for its direct interaction with PSMD14."
37935198
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"Based on previous study that PHD2–3 domain is critical for recruiting NSD2 to chromatin, 8 our results revealed that the interaction between PSMD14 and NSD2 occurs independently of NSD2’s binding to c[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
sparser
"The co-immunoprecipitation assay with nuclear extracts still detected the interaction between PSMD14 and NSD2 upon co-depletion of PSMD1 and PSMD2 ( Figure S1 C), suggesting that the physical interact[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
sparser
"These observations are consistent with the physical association and functional coordination between PSMD14 and NSD2 as well as with transcription activation of RELA by PSMD14-NSD2 complex, supporting [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
reach
"It seems plausible that the aberrant expression of NSD2 and/or PSMD14 can promote a gain of function of PSMD14-NSD2 complex in the nucleus that unleashes an oncogenic epigenetic reprogramming to drive[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
reach
"Exploring the PSMD14-NSD2 complex in diverse physiological and pathological contexts is also crucial for understanding of its multifaceted functions in cell fate determination and therapeutic potentia[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37935198
sparser
"Collectively, these experiments demonstrate that PSMD14 interacts with NSD2 on chromatin via NSD2’s PHD domain and independent of the 19 S RP."
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"21 To explore the biological significance of the physical association of PSMD14 with NSD2, we thus first investigated whether PSMD14 might deubiquitinate thus stabilize NSD2."
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