Blm-s , a BH3-Only Protein Enriched in Postmitotic Immature Neurons, Is Transcriptionally Upregulated by p53 during DNA Damage

Liu, Wei-Wen; Chen, Shih Yu; Cheng, Chia Hsien; Cheng, Hao‐Tsai; Huang, Pei‐Hsin

doi:10.1016/j.celrep.2014.08.050

Cited by 6 publications

(9 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To investigate the function of BLM-s in vivo, we generated Blm-s -knockout ( Blm-s −/− ) mice. Because Blm-s transcript is an isoform of the Blm-l gene and is transcribed via the usage of alternative promoter and TSS located at the 24th intron of the Blm-l genome [ 31 ], we generated a Blm-s -specific knockout by removing the Blm-s genome but preserving the transcription of Blm-l gene (Fig. 1A and see Materials and Methods section).…”

Section: Resultsmentioning

confidence: 99%

“…We have previously reported that BLM-s modulate the survival of immature postmitotic migratory neurons in the developing cortex under the stress of DNA double-strand breaks. RNAi-mediated knockdown of BLM-s in murine embryonic brains protects immature neurons from irradiation-induced apoptosis [ 31 ]. Accordingly, we assessed whether Blm-s −/− embryonic cortex is more resistant to apoptosis provoked by γ-irradiation.…”

Section: Resultsmentioning

confidence: 99%

“…BLM-s is a BH3-only apoptosis sensitizer/derepressor of the BCL-2 family, which consists of >40 members harboring the evolutionarily highly conserved BH domain and plays important roles in the regulation of cell death under various physiological or pathological conditions [ 30 , 31 ]. BLM-s is an isoform encoded by the Blm-l gene (also known as mVps50 [ 32 ], Syndetin [ 33 ], mVps54L [ 34 ], and CCDC132 [ 35 ]) via the usage of alternative promoter and transcriptional start site (TSS) and is transcriptionally upregulated via ATM/p53 and JNK/AP1 signaling pathways triggered by DNA double-strand breaks [ 31 ]. BLM-s is transiently expressed in the postmitotic immature neurons to promote developmental apoptosis during embryonic cortical histogenesis [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

“…BLM-s is an isoform encoded by the Blm-l gene (also known as mVps50 [ 32 ], Syndetin [ 33 ], mVps54L [ 34 ], and CCDC132 [ 35 ]) via the usage of alternative promoter and transcriptional start site (TSS) and is transcriptionally upregulated via ATM/p53 and JNK/AP1 signaling pathways triggered by DNA double-strand breaks [ 31 ]. BLM-s is transiently expressed in the postmitotic immature neurons to promote developmental apoptosis during embryonic cortical histogenesis [ 31 ]. While BLM-s is also expressed in multiple brain regions of adult mice, including the hippocampus, the physiological role of BLM-s in the adult brain is totally unknown.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control

et al. 2022

Self Cite

View full text Add to dashboard Cite

Mood disorders are an important public health issue and recent advances in genomic studies have indicated that molecules involved in neurodevelopment are causally related to mood disorders. BLM-s (BCL-2-like molecule, small transcript isoform), a BH3-only proapoptotic BCL-2 family member, mediates apoptosis of postmitotic immature neurons during embryonic cortical development, but its role in the adult brain is unknown. To better understand the physiological role of Blm-s gene in vivo, we generated a Blm-s-knockout (Blm-s−/−) mouse. The Blm-s−/− mice breed normally and exhibit grossly normal development. However, global depletion of Blm-s is highly associated with depression- and anxiety-related behaviors in adult mutant mice with intact learning and memory capacity. Functional magnetic resonance imaging of adult Blm-s−/− mice reveals reduced connectivity mainly in the ventral dentate gyrus (vDG) of the hippocampus with no alteration in the dorsal DG connectivity and in total hippocampal volume. At the cellular level, BLM-s is expressed in DG granule cells (GCs), and Blm-s−/− mice show reduced dendritic complexity and decreased spine density in mature GCs. Electrophysiology study uncovers that mature vGCs in adult Blm-s−/− DG are intrinsically more excitable. Interestingly, certain genetic variants of the human Blm homologue gene (VPS50) are significantly associated with depression traits from publicly resourced UK Biobank data. Taken together, BLM-s is required for the hippocampal mood control function. Loss of BLM-s causes abnormality in the electrophysiology and morphology of GCs and a disrupted vDG neural network, which could underlie Blm-s-null-associated anxiety and depression.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Contrarily to this report, the present study revealed that MAPKs, including JNK, were constantly activated by TIPE1 overexpression in RAW264.7 cells. Erk, p38 and JNK could regulate mitochondrial functions, including the levels of Bcl-2 family proteins, to influence apoptosis progression (27)(28)(29)(30).…”

Section: C a Bmentioning

confidence: 99%

Tumor necrosis factor α-induced protein 8-like 1 promotes apoptosis by regulating B-cell leukemia/lymphoma-2 family proteins in RAW264.7 cells

Wang¹,

Liu²,

Hu³

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. Although the newly identified protein tumor necrosis factor α-induced protein 8-like 1 (TNFAIP8L1), also known as TIPE1, has been reported to be able to induce apoptosis in human hepatocellular carcinoma cells, the involvement of TIPE1 in apoptosis remains to be elucidated. The present study investigated the pro-apoptotic effect of TIPE1 in an murine macrophage cell line, RAW264.7. The cell apoptosis rate was detected by flow cytometry. The results revealed that overexpressed TIPE1 could directly enhance the apoptosis and the cisplatin-induced cell death of RAW264.7 cells in vitro. Meanwhile, TIPE1 overexpression could suppress tumor growth in vivo. Furthermore, western blotting revealed that overexpressed TIPE1 could upregulate the expression of B-cell leukemia/lymphoma (Bcl)-2 associated X protein (Bax), Bcl-2 interacting killer (Bik) and p53 upregulated modulator of apoptosis (Puma), and activate the mitogen activated protein kinases (MAPKs) signaling pathway. However, western blotting demonstrated that inhibitors of the MAPKs pathway could not decrease the expression of Bax, Bik or Puma. These results indicated that TIPE1 could promote the apoptosis of RAW264.7 cells by upregulating the pro-apoptotic members of the Bcl-2 family of proteins, and that the MAPKs signaling pathway was not involved in the pro-apoptotic effect of TIPE1.

show abstract

Supramolecular Self‐Assembly‐Facilitated Aggregation of Tumor‐Specific Transmembrane Receptors for Signaling Activation and Converting Immunologically Cold to Hot Tumors

Fang

Zhang

et al. 2021

Advanced Materials

View full text Add to dashboard Cite

Supramolecular self‐assembling peptide systems are attracting increasing interest in the field of cancer theranostics. Additionally, transformation of the immunologically cold tumor microenvironment into hot is of great importance for obtaining high antitumor responses for most immunotherapies. However, as far as it is known, there are nearly no studies on self‐assembling peptides reported to be able to convert cold to hot tumors. Herein, a self‐assembling peptide‐based cancer theranostic agent (named DBT‐2FFGYSA) is designed and synthesized, which can target tumor‐specific transmembrane Eph receptor A2 (EphA2) receptors selectively and make the receptors form large aggregates. Such aggregate formation promotes the cross‐phosphorylations among EphA2 receptors, leading to signal transduction of antitumor pathway. As a consequence, DBT‐2FFGYSA can not only visualize EphA2 receptors in a fluorescence turn‐on manner, but also specifically suppress the EphA2 receptor‐overexpressed cancer cell proliferation and tumor growth. What is more, DBT‐2FFGYSA also serves as an effective agent to convert immunologically cold tumors to hot by inducing the immunogenic cell death of EphA2 receptor‐overexpressed cancer cells and recruiting massive tumor‐infiltrating T cells. This study, thus, introduces a new category of agents capable of converting cold to hot tumors by pure supramolecular self‐assembly without any aid of known anticancer drugs.

show abstract

Blm-s , a BH3-Only Protein Enriched in Postmitotic Immature Neurons, Is Transcriptionally Upregulated by p53 during DNA Damage

Cited by 6 publications

References 52 publications

Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control

Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control

Tumor necrosis factor α-induced protein 8-like 1 promotes apoptosis by regulating B-cell leukemia/lymphoma-2 family proteins in RAW264.7 cells

Supramolecular Self‐Assembly‐Facilitated Aggregation of Tumor‐Specific Transmembrane Receptors for Signaling Activation and Converting Immunologically Cold to Hot Tumors

Contact Info

Product

Resources

About