Trim27 confers myeloid hematopoiesis competitiveness by upregulating myeloid master genes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE114579 | GEO | 2018/06/01
REPOSITORIES: GEO
Similar Datasets
Project description:Trim27 confers myeloid hematopoiesis competitiveness by upregulating myeloid master genes
| PRJNA471853 | ENA
Project description:Infectious diseases, such as Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB), remain a global health threat exacerbated by increasing drug resistance. Host-directed therapy (HDT) is a complementing strategy for infection treatment through targeting host immune mechanisms. However, the limited understanding of the host factors and their regulatory mechanisms involved in host immune defense against infections has impeded HDT development. Here, we identify the E3 ubiquitin ligase tripartite motif-containing 27 (TRIM27) elicits host protective immunity against Mtb. Mechanistically, TRIM27 enters host cell nucleus upon Mtb infection to function as a transcription activator of transcription factor EB (TFEB). TRIM27 binds to TFEB promoter and the TFEB transcription factor cAMP responsive element binding protein 1 (CREB1), thus enhancing CREB1-TFEB promoter binding affinity and promoting CREB1 transcription activity towards TFEB, eventually leading to autophagy activation and pathogen clearance. Thus, TRIM27 contributes to host anti-Mtb immunity and targeting TRIM27/CREB1/TFEB axis serves as a promising HDT-based TB treatment.
2024-07-03 | GSE237039 | GEO
Project description:Cancer invasion and metastasis are governed by intricate molecular mechanisms. We demonstrate that TRIM27, an E3 ubiquitin ligase, plays dichotomous roles in cancer depending on its subcellular localization, which is controlled by acetylation/deacetylation at K297 independent of its ligase activity. Acetylation by GCN5 directs TRIM27 to the nucleus, while deacetylation by HDAC4 promotes cytoplasmic localization and cell proliferation. Nuclear TRIM27 binds PARP1 and NELFs, represses PARP1-mediated NELFA ADP-ribosylation, maintains RNA polymerase II pausing, and suppresses PAX6 transcription, thereby inhibiting cancer invasion and metastasis.
2026-04-27 | GSE327188 | GEO
Project description:In an attempt to unravel the functionality and targettability of the non-canonical PRC1.1 Polycomb complex in human leukemogenesis, we dissected the subunit composition of the PRC1.1 complex and show that USP7 and TRIM27 are integral components. USP7 interactome analyses show that PRC1.1 is the predominant Polycomb complex co-precipitating with USP7. USP7 inhibition results in PRC1.1 disassembly and loss of chromatin binding, coinciding with reduced H2AK119ub and H3K27ac levels and diminished gene transcription of active PRC1.1-controlled loci, whereas H3K4me3 levels remain unaffected. TRIM27 and USP7 are reciprocally required for incorporation into PRC1.1, and TRIM27 knockdown partially rescues USP7 inhibitor sensitivity. USP7 inhibitors effectively impair proliferation in (primary) AML cells in vitro, also independent of the USP7-MDM2-TP53 axis, and MLL-AF9-induced leukemia is significantly delayed in vivo in human leukemia xenografts. We propose a model where USP7 counteracts TRIM27 E3 ligase activity, thereby maintaining PRC1.1 integrity and function. Moreover, USP7 inhibition may be a promising new strategy to treat AML patients.
2021-06-14 | PXD018365 | Pride
Project description:Cancer invasion and metastasis are orchestrated by intricate molecular mechanisms that remain not fully understood. We have identified that the tripartite motif-containing protein 27 (TRIM27), typically known as an E3 ubiquitin ligase, plays dichotomous roles in cancer progression. These roles are determined by its subcellular localization, which is regulated by acetylation and deacetylation at lysine 297 (K297) independently of its ubiquitin ligase activity. Acetylation by general control non-repressed protein 5 (GCN5) directs TRIM27 to the nucleus, where it inhibits cancer cell invasion and metastasis by modulating the transcription of paired box 6 (PAX6). Conversely, deacetylation by histone deacetylase 4 (HDAC4) results in cytoplasmic localization, promoting cell proliferation and tumor growth. In the nucleus, TRIM27 binds to poly (ADP-ribose) polymerase 1 (PARP1) and negative elongation factors (NELFs), repressing PARP1-mediated mono-ADP-ribosylation of NELFA, thereby preventing the release of RNA polymerase II from transcriptional pausing, and leading to transcriptional repression of PAX6. Furthermore, we demonstrate that treatment with the PARP1 inhibitor Olaparib limits the metastasis of cancer cells lacking breast cancer gene (BRCA) mutations, uncovering a previously overlooked therapeutic potential. Importantly, the combination of Olaparib and the HDAC4 inhibitor Tasquinimod synergistically inhibits cancer metastasis. Collectively, these findings reveal a complex interplay of post-translational modifications that dictate the subcellular localization and biological functions of TRIM27, highlighting novel strategies for effective cancer treatment.
2026-04-27 | GSE328543 | GEO
Project description:Cancer invasion and metastasis are orchestrated by intricate molecular mechanisms that remain not fully understood. We have identified that the tripartite motif-containing protein 27 (TRIM27), typically known as an E3 ubiquitin ligase, plays dichotomous roles in cancer progression. These roles are determined by its subcellular localization, which is regulated by acetylation and deacetylation at lysine 297 (K297) independently of its ubiquitin ligase activity. Acetylation by general control non-repressed protein 5 (GCN5) directs TRIM27 to the nucleus, where it inhibits cancer cell invasion and metastasis by modulating the transcription of paired box 6 (PAX6). Conversely, deacetylation by histone deacetylase 4 (HDAC4) results in cytoplasmic localization, promoting cell proliferation and tumor growth. In the nucleus, TRIM27 binds to poly (ADP-ribose) polymerase 1 (PARP1) and negative elongation factors (NELFs), repressing PARP1-mediated mono-ADP-ribosylation of NELFA, thereby preventing the release of RNA polymerase II from transcriptional pausing, and leading to transcriptional repression of PAX6. Furthermore, we demonstrate that treatment with the PARP1 inhibitor Olaparib limits the metastasis of cancer cells lacking breast cancer gene (BRCA) mutations, uncovering a previously overlooked therapeutic potential. Importantly, the combination of Olaparib and the HDAC4 inhibitor Tasquinimod synergistically inhibits cancer metastasis. Collectively, these findings reveal a complex interplay of post-translational modifications that dictate the subcellular localization and biological functions of TRIM27, highlighting novel strategies for effective cancer treatment.
2026-04-27 | GSE328799 | GEO
Project description:Identification of the specific acetylation sites on GST-TRIM27 modified by HA-GCN5 in vitro and the specific nuclear interaction partners of TRIM27 using mass spectrometry
2026-03-11 | PXD075537 |
Project description:These data accompany our publication "RIT1 oncoproteins escape LZTR1-mediated proteolysis" (Castel P., et al. Science, 2019).
Experiment 1:
Identification of LZTR1 as an interacting partner of RIT1
Q Exactive Plus
P20161208-02 FLAG GFP
P20161208-03 FLAG RIT1
LTQ Orbitrap Velos
V20170407-01 GST empty vector
V20170407-03 GST RIT1
V20170407-06 HA empty vector
V20170407-07 HA RIT1
Experiment 2:
Identification of K135 and K187 ubiquitination sites in RIT1
Q Exactive Plus
P20180408-01 FLAG-RIT1 / empty vector / empty vector (replicate 1)
P20180408-02 FLAG-RIT1 / LZTR1 / empty vector (replicate 1)
P20180408-03 FLAG-RIT1 / empty vector / TUBE (replicate 1)
P20180408-04 FLAG-RIT1 / LZTR1 / TUBE (replicate 1)
P20180408-06 GST-RIT1 / empty vector / empty vector (replicate 1)
P20180408-07 GST-RIT1 / LZTR1 / empty vector (replicate 1)
P20180408-08 GST-RIT1 / empty vector / TUBE (replicate 1)
P20180408-09 GST-RIT1 / LZTR1 / TUBE (replicate 1)
P20180408-11 GST-RIT1 / empty vector / empty vector (replicate 2)
P20180408-12 GST-RIT1 / LZTR1 / empty vector (replicate 2)
P20180408-13 GST-RIT1 / empty vector / TUBE (replicate 2)
P20180408-14 GST-RIT1 / LZTR1 / TUBE (replicate 2)
P20180408-16 FLAG-RIT1 / empty vector / empty vector (replicate 2)
P20180408-17 FLAG-RIT1 / LZTR1 / empty vector (replicate 2)
P20180408-18 FLAG-RIT1 / empty vector / TUBE (replicate 2)
P20180408-32 FLAG-RIT1 / LZTR1 / TUBE (replicate 2)
2019-02-14 | MSV000083444 | MassIVE
Project description: Not available
| S-EPMC3255705 | biostudies-literature