Table represents ratio and percentage for overexpression and underexpression in relation to the total number of analyses available in the database. Fat facets interacts with vasa in the Drosophila pole plasm and protects it from degradation. Regarding its pro-apoptotic activities, three independent lines of evidence implicate USP9X. Deubiquitinase inhibition by small-molecule WP triggers aggresome formation and tumor cell apoptosis. There are approximately 95 DUBs encoded by the human genome [ 3 ]. At the top of your Chrome window, near the web address, click the green lock labeled Secure. Ongoing large-scale cancer sequencing projects are predicted to reveal further genetic evidence of the involvement of USP9X in cancer.
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Additional indirect evidence for the involvement of USP9X in neurodevelopmental disorders comes from its interaction with doublecortin DCX.
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The landscape of somatic copy-number alteration across human cancers. Hershko A, Ciechanover A. Above the schematic is a scale in amino acidsdubays localisation of variants associated with ID 18 and a histogram of variants found in cancer samples cBioportal. USP9X downregulation renders breast cancer cells resistant to tamoxifen. Chromosome alignment and segregation regulated by ubiquitination 6 survivin. Mutations in DCX cause defective neuronal growth and migration leading to lissencephaly in males and sub-cortical band heterotopia in females, with associated epilepsy and intellectual disability features [ 8081 ].
Transcription factor with critical roles in embryonic CNS development. Likewise, the transcription factor p53 has been reported to influence USP9X expression [ 67 ], which might provide an avenue to target certain cancers. MCL1 is a member of the anti-apoptotic BCL2 family that is essential for promoting the survival of multiple cell types [ 55 — 57 ].
Support Center Support Center. Therefore, the activity and functional relevance of all USPs is highly context specific, dependent on the activity of the upstream enzymes, such as E3 ubiquitin ligase or kinases, performing the preceding PTMs. FAM deubiquitylating enzyme is essential for preimplantation mouse embryo development. Dubway Studios Claimed This business has been claimed by the owner or a representative. A quest for human and mouse embryonic stem cell-specific proteins.
In aggregate, it is clear that USP9X could contribute to the expressivity and outcomes of neurodegenerative disorders; however, the evidence thus far has been mostly associative. Hicke L, Dunn R.
In cis, the ubiquitylation status of cargo proteins e. Faf regulation of Lqf is essential for a specific endocytic event as opposed to bulk endocytosis required for the competence of the Notch ligand Delta to signal [ 34 dubwayys. The functional interactome landscape of the human histone deacetylase family. In the MPTP 1-methylphenyl-1,2,3,6 tetrahydropyridine -induced acute PD mouse model, however, USP9X expression was significantly upregulated in all areas of the brain, perhaps reflecting a cellular response to toxicity [ 87 ].
The largest family is the ubiquitin-specific proteases USPwhich is substrate specific and precisely regulates cellular processes. Functional dissection of the TBK1 molecular network. At the top of your Firefox window, to the left of the web address, you should see a green lock.
The complexities of its function and regulation will be challenging to dissect; however, this accomplishment will be accompanied by new exciting insights into human biology dubsays disease.
USP9X in disease Many of the above descriptions on the molecular, cell and developmental processes regulated by USP9X have also been described in the context of pathological mechanisms underlying various human diseases.
La FAM fatale: USP9X in development and disease
A large part of tissue development regulation and homoeostasis concerns the precise control of cell numbers, morphology and function in response to local or systemic signals.
Helping Families Devastated by Cancer. The complex and dynamic expression of USP9X and its substrates suggests that this task will be a daunting one, but investigations of the effects of rare genetic variants associated with neurological disorders have begun to provide important insights and should remain a focus of future research.
Structural information of USP9X. Doublecortin interacts with the ubiquitin protease DFFRX, which associates with microtubules in neuronal processes. USP9X also interacts with the anti-apoptotic factor survivin [ 1361 ], although the relevance of this interaction in the context of apoptosis has dubwsys been addressed. In mammalian cells, USP9X has been shown to regulate the levels of stress-sensing pro-apoptotic kinases that initiate the apoptotic JNK signalling cascade.
Ongoing large-scale cancer sequencing projects are predicted to reveal further genetic evidence of the involvement of USP9X in cancer. USP9X in neurodevelopmental disorders and neurodegeneration Consistent with its functions during mouse embryonic brain development, USP9X has been implicated in a number of human neurodevelopmental disorders.