Disease relevance of YEATS4

• Expression, cellular distribution and protein binding of the glioma amplified sequence (GAS41), a highly conserved putative transcription factor [1].
• The glioma amplified sequence 41 (GAS41) was previously isolated by microdissection mediated cDNA capture from the glioblastoma multiforme cell line TX3868 and shown to be frequently amplified in human gliomas [1].
• In neuroblastoma however, GAS41 was found in the nucleoli but not in the nucleoplasm [1].

High impact information on YEATS4

• GAS41 is a common subunit of the TIP60 and SRCAP complexes and is essential for cell growth and viability [2].
• Our data suggest that GAS41 plays a role in repressing the p53 tumor suppressor pathway during the normal cell cycle by a TIP60-independent mechanism [2].
• Here, we report that GAS41 is required for repression of the p53 tumor suppressor pathway during normal cellular proliferation [2].
• The MLL fusion partner AF10 binds GAS41, a protein that interacts with the human SWI/SNF complex [3].
• The leucine zipper interacted with GAS41, a protein previously identified as the product of an amplified gene in a glioblastoma [3].

Biological context of YEATS4

• GAS41 is required for repression of the p53 tumor suppressor pathway during normal cellular proliferation [2].
• With GAS41 being the first gene found with increased copy number in low grade glioma, this study provides the first evidence that gene amplification can occur in early tumor development [4].
• Targeted disruption of the GAS41 gene encoding a putative transcription factor indicates that GAS41 is essential for cell viability [5].
• Inactivation of this promoter by tetracycline withdrawal results in rapid depletion of GAS41, causing a significant decrease in RNA synthesis and subsequently cell death [5].
• However, a homozygous GAS41-/- cell line with both GAS41 alleles disrupted was not obtained following the second round of transfection, indicating that the GAS41 gene is essential for cell viability [5].

Anatomical context of YEATS4

• After generating polyclonal antibodies we found GAS41 protein expression in the nucleus of the TX3868 cell line by Western blot analysis and immunofluorescence microscopy [1].
• Using this assay, we show that protein kinase activity and the NuMA-binding protein LGN regulate the dynamic exchange of NuMA on microtubule asters [6].

Physical interactions of YEATS4

• Significantly, we demonstrate that TACC2 interacts with GAS41 and the SWI/SNF chromatin remodeling complex [7].

Other interactions of YEATS4

• However, during evolution, the TACC proteins have now acquired the ability to directly interact with components of these complexes (such as the LSm proteins, nuclear hormone receptors, GAS41, and transcription factors) [8].

Analytical, diagnostic and therapeutic context of YEATS4

• A human multiple-tissue Northern blot revealed ubiquitous expression of GAS41 with the highest expression in human brain [1].
• In vitro GAS41 bound to the C-terminal part of the rod region of NuMA, as shown by dot overlay and by surface plasmon resonance measurements [9].
• Finally, electrophoretic mobility shift assay (EMSA) suggested that GAS41 enhances the DNA-binding activity of AP-2beta [10].

References