RGD Reference Report - Involvement of p21 (waf1) in merlin deficient sporadic vestibular schwannomas. - Rat Genome Database

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Involvement of p21 (waf1) in merlin deficient sporadic vestibular schwannomas.

Authors: Wu, H  Chen, Y  Wang, ZY  Li, W  Li, JQ  Zhang, L  Lu, YJ 
Citation: Wu H, etal., Neuroscience. 2010 Sep 29;170(1):149-55. doi: 10.1016/j.neuroscience.2010.06.051. Epub 2010 Jul 1.
RGD ID: 8661792
Pubmed: PMID:20600642   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuroscience.2010.06.051   (Journal Full-text)

Previous studies have demonstrated that merlin acts as a tumor suppressor by blocking Ras-mediated signaling. However, the mechanism by which merlin controls cell proliferation has remained obscure. Here we show that merlin deficient tumors exhibited loss of p21, concomitant with elevated CDKs/cyclin D1 levels in sporadic vestibular schwannomas (VS) from clinic patients. Likewise, silencing of merlin gene expression in the cell lines resulted in down-regulation of p21. Furthermore, we find that merlin-enhanced p21 protein stability, rather than increased RNA accumulation, was responsible for the elevated p21 levels. Interestingly, p21 was required to maintain merlin levels and the inhibitory effect of merlin on Ras signaling was partially overridden by knockdown of p21. Consistent with the observation that over-expression of merlin arrested cell growth at G1-phase, the current study indicates that merlin exerts its antiproliferative effect, at least in part, by maintaining p21 expression, and loss of p21 is a prominent feature of merlin deficient schwannomas.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
acoustic neuroma  IEP 8661792mRNA and protein:decreased expression:myelinated nerve:RGD 
acoustic neuroma  ISOCDKN1A (Homo sapiens)8661792; 8661792mRNA and protein:decreased expression:myelinated nerve:RGD 
acoustic neuroma  IEP 8661792protein:decreased expression:myelinated nerve:RGD 
acoustic neuroma  ISONF2 (Homo sapiens)8661792; 8661792protein:decreased expression:myelinated nerve:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cdkn1a  (cyclin-dependent kinase inhibitor 1A)
Nf2  (NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor)

Genes (Mus musculus)
Cdkn1a  (cyclin dependent kinase inhibitor 1A)
Nf2  (neurofibromin 2)

Genes (Homo sapiens)
CDKN1A  (cyclin dependent kinase inhibitor 1A)
NF2  (NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor)


Additional Information