Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P10412 (
H1.4
)
75
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Background:
Osteosarcoma
is prevalent in children and adolescents.
H1.4
modification is involved in various types of cancers. Ras pathway is often activated in human cancers. Herein, we explored the effects of Ras pathway through
H1.4
S35ph
.
Methods:
Osteosarcoma
cancer cell line MG-63 was transfected with Ras gene with G12V and Y40C site mutation. The phosphorylation of
H1.4
S35
and AKT was detected by Western blot. Cell viability, cell colonies and migration were analyzed by MTT assay, soft-agar colony formation assay and Transwell assay, respectively. The expression of Ras pathway downstream factors and PKA was detected by qRT-PCR. The relationship between Ras and downstream factors was detected by ChIP. The cell cycle progression was measured by flow cytometry.
Results:
Transfection with Ras
G12V/Y40C
decreased
H1.4
S35ph
expression while switched on p-AKT
Ser473
. Ras
G12V/Y40C
increased cell viability, colony numbers and migration while
H1.4
S35E
(
H1.4
S35ph
overexpression) led to the opposite results. The regulation of Ras
G12V/Y40C
and
H1.4
S35E
on Ras downstream factors was contrary to each other. Results demonstrated a positive relationship between PKA with
H1.4
S35ph
with Ras
G12V/Y40C
down-regulated both. However, PKA and MDM2 revealed negative regulation with Ras
G12V/Y40C
transfection up-regulated MDM2.
Conclusion:
Ras
G12V/Y40C
-PI3K/AKT signal pathway decreased
H1.4
S35ph
through down-regulation of PKA while up-regulation of MDM2 in MG-63 cells. Highlights
H1.4
S35ph
is regulated by K-Ras
G12V/Y40
-PI3K/AKT in MG-63 cells; Overexpression of
H1.4
S35ph
regulates MG-63 cell growth;
H1.4
S35ph
regulates Ras downstream factors; K-Ras
G12V/Y40C
-PI3K/AKT activity induces PKA degradation to down-regulate
H1.4
S35ph
; K-Ras
G12V/Y40C
-PI3K/AKT activity involves in PKA degradation via MDM2.
...
PMID:K-Ras
G12V/Y40C
-PI3K/AKT pathway regulates H1.4
S35ph
through PKA to promote the occurrence and development of osteosarcoma cancer. 3244 Nov 46
