Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatic inactivation of PTEN occurs in different human tumors including glioblastoma, endometrial carcinoma and prostate carcinoma. Germline mutations in PTEN result in a range of phenotypic abnormalities that occur with variable penetrance, including neurological features such as macrocephaly, seizures, ataxia and Lhermitte-Duclos disease (also described as dysplastic gangliocytoma of the cerebellum). Homozygous deletion of Pten causes embryonic lethality in mice. To investigate function in the brain, we used Cre-loxP technology to selectively inactivate Pten in specific mouse neuronal populations. Loss of Pten resulted in progressive macrocephaly and seizures. Neurons lacking Pten expressed high levels of phosphorylated Akt and showed a progressive increase in soma size without evidence of abnormal proliferation. Cerebellar abnormalities closely resembled the histopathology of human Lhermitte-Duclos disease. These results indicate that Pten regulates neuronal size in vivo in a cell-autonomous manner and provide new insights into the etiology of Lhermitte-Duclos disease.
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PMID:Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease. 1172 27

RING finger protein 135 (RNF135, also named Riplet or REUL) exerts multiple biological functions and its C-terminal PRY-SPRY/B30.2 domain is indispensable for most of these functions. RNF135 interacts with RIG-I (retinoic acid-inducible gene-I) via the PRY-SPRY domain and ubiquitinates RIG-I to promote innate anti-viral signaling, while mutations in the RNF135 gene can cause the Macrocephaly, macrosomia, facial dysmorphism (MMFD) syndrome, and RNF135 reportedly regulates the proliferation of glioblastoma cells as well as tongue cancer cells. Nevertheless, structure of full-length RNF135 or its PRY-SPRY domain has not been determined, and structural basis for molecular interactions involving RNF135 is largely unknown. Here we report the backbone 1H, 13C, and 15N chemical shift assignments of the PRY-SPRY domain of RNF135 and the secondary structure elements predicted based on chemical shifts, as well as the perturbations caused by the R286H mutation that is associated with MMFD syndrome. We found that the mutation did not alter the gross structure of the PRY-SPRY domain, so it may have impaired RNF135 function by affecting protein-protein interactions mediated by the domain.
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PMID:Backbone 1H, 13C, and 15N resonance assignments of the PRY-SPRY domain of RNF135. 3106 57