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:C0278883 (
metastatic melanoma
)
6,224
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
N
6
-Methyladenosine (m
6
A) in messenger RNA (mRNA) regulates its stability, splicing, and translation efficiency. Here, we explored how the expression levels of small GTPase proteins are regulated by m
6
A modulators. We employed a high-throughput scheduled multiple-reaction monitoring (MRM)-based targeted proteomic approach to quantify systemically the changes in expression of small GTPase proteins in cells upon genetic ablation of METTL3 (the catalytic subunit of the major m
6
A methyltransferase complex), m
6
A demethylases (ALKBH5 and FTO), or m
6
A reader proteins (YTHDF1, YTHDF2, and
YTHDF3
). Depletions of METTL3 and ALKBH5 resulted in substantially diminished and augmented expression, respectively, of a subset of small GTPase proteins, including RHOB and RHOC. Our results also revealed that the stability of RHOB mRNA is significantly increased in cells depleted of METTL3, suggesting an m
6
A-elicited destabilization of this mRNA. Those small GTPases that are targeted by METTL3 and/or ALKBH5 also displayed higher discrepancies between protein and mRNA expression in paired primary/
metastatic melanoma
or colorectal cancer cells than those that are not. Together, this is the first comprehensive analysis of the alterations in small GTPase proteome regulated by epitranscriptomic modulators of m
6
A, and our study suggests the potential of an alternative therapeutic approach to target the currently "undruggable" small GTPases.
...
PMID:Proteome-wide Interrogation of Small GTPases Regulated by
N
6
-Methyladenosine Modulators. 3256 49
