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: UMLS:C0026986 (
myelodysplastic syndrome
)
14,926
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Ribosomal protein (RP) L23 is a negative regulator of cellular apoptosis, and RPL23 overexpression is associated with abnormal apoptotic resistance in CD34+ cells derived from patients with higher-risk
myelodysplastic syndrome
(
MDS
). However, the mechanism underlying RPL23-induced apoptotic resistance in higher-risk
MDS
patients is poorly understood. In this study, we showed that reduced RPL23 expression led to suppressed cellular viability, increased apoptosis and G1-S cell cycle arrest. Gene microarray analysis comparing RPL23-knockdown and control cells identified an array of differentially expressed genes, of which,
Miz-1
, was upregulated with transactivation of the cell cycle inhibitors p15
Ink4b
and p21
Cip1
, and
Miz-1
's functional repressor, c-Myc, was downregulated. Cells derived from higher-risk
MDS
patients demonstrated consistently increased expression of RPL23 and c-Myc and decreased
Miz-1
expression compared with cells from lower-risk patients. In conclusion,
Miz-1
-dependent induction of p15
Ink4b
and p21
Cip1
was depressed with decreased
Miz-1
and increased c-Myc expression under conditions of elevated RPL23 expression, leading to apoptotic resistance in higher-risk
MDS
patients. Because RPL23 is encoded by a target gene of c-Myc, the RPL23/
Miz-1
/c-Myc regulatory circuit provides a feedback loop that links efficient RPL23 expression with c-Myc's function to suppress
Miz-1
-induced Cdk inhibitors and thereby leads to apoptotic resistance in higher-risk
MDS
patients.
...
PMID:Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome. 2853 3
