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:C0026764 (
multiple myeloma
)
36,148
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
RNF6
, a RING-type ubiquitin ligase, has been identified as an oncogene in various cancers but its role in
multiple myeloma
(MM) remains elusive. In the present study we first showed that the expression levels of
RNF6
in MM were significantly elevated compared with the bone marrow cells of healthy donors. Overexpression of
RNF6
in LP1 and PRMI-8266 MM cell lines promoted cell proliferation, whereas knockdown of
RNF6
led to apoptosis of MM cells. Furthermore, we revealed that
RNF6
, as a ubiquitin ligase, interacted with glucocorticoid receptor (GR) and induced its K63-linked polyubiquitination. Different from current knowledge,
RNF6
increased GR stability at both endogenous and exogenous contexts. Such an action greatly promoted GR transcriptional activity, which was confirmed by luciferase assays and by the increased expression levels of prosurvival genes including Bcl-xL and Mcl-1, two typical downstream genes of the GR pathway. Consistent with these findings, ectopic expression of
RNF6
in MM cells conferred resistance to dexamethasone, a typical anti-
myeloma
agent. In conclusion, we demonstrate that
RNF6
promotes MM cell proliferation and survival by inducing atypical polyubiquitination to GR, and
RNF6
could be a promising therapeutic target for the treatment of MM.
...
PMID:RNF6 promotes myeloma cell proliferation and survival by inducing glucocorticoid receptor polyubiquitination. 3164 58
