scholarly journals A Human Protein Complex Homologous to the Drosophila MSL Complex Is Responsible for the Majority of Histone H4 Acetylation at Lysine 16

2005 ◽  
Vol 25 (21) ◽  
pp. 9175-9188 ◽  
Author(s):  
Edwin R. Smith ◽  
Christelle Cayrou ◽  
Rong Huang ◽  
William S. Lane ◽  
Jacques Côté ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Rna Interference ◽  
Histone Acetyltransferase ◽  
Histone H4 ◽  
M Cell ◽  
Cycle Arrest ◽  
Histone H4 Acetylation ◽  
Msl Complex ◽  
Host Cell Factor 1

ABSTRACT We describe a stable, multisubunit human histone acetyltransferase complex (hMSL) that contains homologs of the Drosophila dosage compensation proteins MOF, MSL1, MSL2, and MSL3. This complex shows strong specificity for histone H4 lysine 16 in chromatin in vitro, and RNA interference-mediated knockdown experiments reveal that it is responsible for the majority of H4 acetylation at lysine 16 in the cell. We also find that hMOF is a component of additional complexes, forming associations with host cell factor 1 and a protein distantly related to MSL1 (hMSL1v1). We find two versions of hMSL3 in the hMSL complex that differ by the presence of the chromodomain. Lastly, we find that reduction in the levels of hMSLs and acetylation of H4 at lysine 16 are correlated with reduced transcription of some genes and with a G2/M cell cycle arrest. This is of particular interest given the recent correlation of global loss of acetylation of lysine 16 in histone H4 with tumorigenesis.

scholarly journals Activation Domain-Specific and General Transcription Stimulation by Native Histone Acetyltransferase Complexes

1999 ◽  
Vol 19 (1) ◽  
pp. 855-863 ◽  
Author(s):  
Keiko Ikeda ◽  
David J. Steger ◽  
Anton Eberharter ◽  
Jerry L. Workman
Keyword(s):  
Histone Acetyltransferase ◽  
Regulation Of Transcription ◽  
Dependent Manner ◽  
Saga Complex ◽  
Histone H4 ◽  
Activation Domain ◽  
Activation Domains ◽  
Nucleosomal Array ◽  
Histone H4 Acetylation

ABSTRACT Recent progress in identifying the catalytic subunits of histone acetyltransferase (HAT) complexes has implicated histone acetylation in the regulation of transcription. Here, we have analyzed the function of two native yeast HAT complexes, SAGA (Spt-Ada-Gcn5 Acetyltransferase) and NuA4 (nucleosome acetyltransferase of H4), in activating transcription from preassembled nucleosomal array templates in vitro. Each complex was tested for the ability to enhance transcription driven by GAL4 derivatives containing either acidic, glutamine-rich, or proline-rich activation domains. On nucleosomal array templates, the SAGA complex selectively stimulates transcription driven by the VP16 acidic activation domain in an acetyl coenzyme A-dependent manner. In contrast, the NuA4 complex facilitates transcription mediated by any of the activation domains tested if allowed to preacetylate the nucleosomal template, indicating a general stimulatory effect of histone H4 acetylation. However, when the extent of acetylation by NuA4 is limited, the complex also preferentially stimulates VP16-driven transcription. SAGA and NuA4 interact directly with the VP16 activation domain but not with a glutamine-rich or proline-rich activation domain. These data suggest that recruitment of the SAGA and NuA4 HAT complexes by the VP16 activation domain contributes to HAT-dependent activation. In addition, extensive H4/H2B acetylation by NuA4 leads to a general activation of transcription, which is independent of activator-NuA4 interactions.

scholarly journals Sodium orthovanadate inhibits growth of acute leukemia HL60 cells and HL60/A cells in vitro

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Lulu Zhang ◽  
Nan Wei ◽  
Guoying Guan ◽  
Tao Song ◽  
Yingying Xu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Leukemia ◽  
Leukemia Cell ◽  
Sodium Orthovanadate ◽  
M Cell ◽  
Hl60 Cells ◽  
Cycle Arrest ◽  
A Cells ◽  
Leukemia Cell Lines

Abstract Vanadium is an ultratrace element. The transition metal vanadium, widely exists in the environment and exhibits various biological and physiological effects in the human body, yet with no presently known specific physiological function in mammals. Sodium orthovanadate (SOV) is a kind of vanadium compound. SOV has shown promising antineoplastic activity in several human cancers. But the effects of SOV on acute promyelocytic leukemia (APL) are still unknown. In the present study, for the first time, we found that SOV could inhibit proliferation, induce G2/M cell cycle arrest and apoptosis, and could inhibit autophagy of acute leukemia cell lines in vitro. Thus, our findings suggest that SOV could effectively suppress the growth of acute leukemia HL60 cells and HL60/A cells through the regulations of proliferation, cell cycle, apoptosis and autophagy, and thus may act as a potential therapeutic agent in APL treatment.

Effect of Marsdenia tenacissima extract on G2/M cell cycle arrest by upregulating 14-3-3σ and downregulating c-myc in vitro and in vivo

2019 ◽  
Vol 11 (2) ◽  
pp. 169-176 ◽  
Author(s):  
Li Sun ◽  
Qurat UI Ain ◽  
Ying-sheng Gao ◽  
Ghulam Jilany Khan ◽  
Sheng-tao Yuan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
M Cell ◽  
Cycle Arrest ◽  
Marsdenia Tenacissima

scholarly journals Romidepsin Induces G2/M Phase Arrest and Apoptosis in Cholangiocarcinoma Cells

2020 ◽  
Vol 19 ◽  
pp. 153303382096075
Author(s):  
Pihong Li ◽  
Luguang Liu ◽  
Xiangguo Dang ◽  
Xingsong Tian
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Antitumor Effect ◽  
Caspase 3 ◽  
M Cell ◽  
Cycle Arrest ◽  
Phase Arrest ◽  
M Phase

Background: Cholangiocarcinoma (CCA) is an extremely intractable malignancy since most patients are already in an advanced stage when firstly discovered. CCA needs more effective treatment, especially for advanced cases. Our study aimed to evaluate the effect of romidepsin on CCA cells in vitro and in vivo and explore the underlying mechanisms. Methods: The antitumor effect was determined by cell viability, cell cycle and apoptosis assays. A CCK-8 assay was performed to measure the cytotoxicity of romidepsin on CCA cells, and flow cytometry was used to evaluate the effects of romidepsin on the cell cycle and apoptosis. Moreover, the in vivo effects of romidepsin were measured in a CCA xenograft model. Results: Romidepsin could reduce the viability of CCA cells and induce G2/M cell cycle arrest and apoptosis, indicating that romidepsin has a significant antitumor effect on CCA cells in vitro. Mechanistically, the antitumor effect of romidepsin on the CCA cell lines was mediated by the induction of G2/M cell cycle arrest and promotion of cell apoptosis. The G2/M phase arrest of the CCA cells was associated with the downregulation of cyclinB and upregulation of the p-cdc2 protein, resulting in cell cycle arrest. The apoptosis of the CCA cells induced by romidepsin was attributed to the activation of caspase-3. Furthermore, romidepsin significantly inhibited the growth of the tumor volume of the CCLP-1 xenograft, indicating that romidepsin significantly inhibited the proliferation of CCA cells in vivo. Conclusions: Romidepsin suppressed the proliferation of CCA cells by inducing cell cycle arrest through cdc2/cyclinB and cell apoptosis by targeting caspase-3/PARP both in vitro and in vivo, indicating that romidepsin is a potential therapeutic agent for CCA.

scholarly journals The therapeutic effectiveness of 177Lu-lilotomab in B-cell non-Hodgkin lymphoma involves modulation of G2/M cell cycle arrest

Leukemia ◽  
2019 ◽  
Vol 34 (5) ◽  
pp. 1315-1328 ◽  
Author(s):  
Alexandre Pichard ◽  
Sara Marcatili ◽  
Jihad Karam ◽  
Julie Constanzo ◽  
Riad Ladjohounlou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Growth ◽  
B Cell ◽  
Cell Cycle Arrest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Growth Delay ◽  
M Cell ◽  
Cycle Arrest

AbstractSome patients with B-cell non-Hodkin lymphoma Lymphoma (NHL) become refractory to rituximab (anti-CD20 antibody) therapy associated with chemotherapy. Here, the effect of the anti-CD37 antibody-radionuclide conjugate lutetium-177 (177Lu)-lilotomab (Betalutin®) was investigated in preclinical models of NHL. In SCID mice bearing DOHH2 (transformed follicular lymphoma, FL) cell xenografts, 177Lu-lilotomab significantly delayed tumor growth, even at low activity (100 MBq/kg). In athymic mice bearing OCI-Ly8 (diffuse large B-cell lymphoma, DLBCL) or Ramos (Burkitt’s lymphoma) cell xenografts, 177Lu-lilotomab activity had to be increased to 500 MBq/kg to show a significant tumor growth delay. Clonogenic and proliferation assays showed that DOHH2 cells were highly sensitive to 177Lu-lilotomab, while Ramos cells were the least sensitive, and U2932 (DLBCL), OCI-Ly8, and Rec-1 (mantle cell lymphoma) cells displayed intermediate sensitivity. The strong 177Lu-lilotomab cytotoxicity observed in DOHH2 cells correlated with reduced G2/M cell cycle arrest, lower WEE-1- and MYT-1-mediated phosphorylation of cyclin-dependent kinase-1 (CDK1), and higher apoptosis. In agreement, 177Lu-lilotomab efficacy in vitro, in vivo, and in patient samples was increased when combined with G2/M cell cycle arrest inhibitors (MK-1775 and PD-166285). These results indicate that 177Lu-lilotomab is particularly efficient in treating tumors with reduced inhibitory CDK1 phosphorylation, such as transformed FL.

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