Journal
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume 41, Issue 6, Pages 3366-3378Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2018.3519
Keywords
c-Myc; B-lineage acute lymphoblastic leukemia; cyclin D kinase 1; cyclin B1; G(2); M arrest; histone H4 acetylation
Categories
Funding
- National Nature Science Foundation of China [31570797, 31270864, 30972675, 31101717]
- Science and Technology Planning Project of Dalian City [2010J21DW011]
- Natural Science Foundation of Liaoning Province [2015020253]
Ask authors/readers for more resources
Overexpression of c-Myc is involved in the tumorigenesis of B-lineage acute lymphoblastic leukemia (B-ALL), but the mechanism is not well understood. In the present study, a c-Myc-knockdown model (Raji-KD) was established using Raji cells, and it was indicated that c-Myc regulates the expression of genes associated with cell cycle progression in G(2)/M-phase, cyclin D kinase (CDK)1 and cyclin B1, by modulating 60 kDa Tat-interactive protein (TIP60)/males absent on the first (MOF)-mediated histone H4 acetylation (AcH4), which was then completely restored by re-introduction of the c-Myc gene into the Raji-KD cells. The expression of CDK1 and cyclin B1 was markedly suppressed in Raji-KD cells, resulting in G(2)/M arrest. In comparison to Raji cells, the proliferation of Raji-KD cells was significantly reduced, and it was recovered via re-introduction of the c-Myc gene. In the tumorigenesis assays, the loss of c-Myc expression significantly suppressed Raji cell-derived lymphoblastic tumor formation. Although c-Myc also promotes Raji cell apoptosis via the caspase-3-associated pathway, CDK1/cyclin B1-dependent-G2/M cell cycle progression remains the major driving force of c-Myc-controlled tumorigenesis. The present results suggested that c-Myc regulates cyclin B1- and CDK1-dependent G(2)/M cell cycle progression by TIP60/MOF-mediated AcH4 in Raji cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available