====== CUX1 ======

{{ ::cux1.png?500|}}

Cut Like homeobox 1 (CUX1), which encodes an auxiliary factor in [[base excision repair]], resides on 7q22.1, the most frequently and highly amplified chromosomal region in [[glioblastoma]]s.

It is expressed in the upper layer of the [[cortex]] and participates in [[DNA replication]], [[cell cycle]] control, and [[DNA repair]]. It has been shown to be involved in the proliferation of various types of solid [[tumor]]s. 

The aims of a study of Wu et al. from the [[Linyi People's Hospital]], [[Qingdao]] University, [[Weifang]] Medical University, [[Taishan]] Medical University, [[Binzhou]] Medical University, were to explore the relationship between CUX1 expression and the [[glioma outcome]] by performing a series of functional experiments and [[bioinformatics]]. Firstly, they found that CUX1 expression levels differed among patients with different grades of [[glioma]]s, and they were significantly correlated with the [[prognosis]] of [[glioma]] patients according to an analysis of data from a public [[database]]. qRT-PCR, [[western blot]]ting, and immunohistochemical analysis of CUX1 were performed to demonstrate that the expression of CUX1 was positively correlated with the glioma [[WHO grade]] (P < 0.05) and several malignant clinical pathological parameters, including [[Ki67]] and [[P53]]mut. In addition, the multivariate [[Cox regression]] and [[Kaplan-Meier]] curves showed that CUX1 expression exerted predictive value for [[overall survival]]. Finally, to further investigate the functions of CUX1, they identified CUX1-associated genes and, though GO/KEGG analysis, their associated biological functions and [[signaling pathway]]s; the results suggested that the activity of CUX1 might be exerted via the [[JAK-STAT signaling pathway]] or other key regulators of the [[cell cycle]] to promote proliferation, inflammation, and chemotherapy resistance in glioma. Taken together, these results indicate that CUX1 is a potential [[biomarker]] of malignancy and prognosis and may serve as a potential therapeutic target for glioma patients.
((Wu X, Feng F, Yang C, Zhang M, Cheng Y, Zhao Y, Wang Y, Che F, Zhang J, Heng
X. Upregulated Expression of CUX1 Correlates with Poor Prognosis in Glioma
Patients: a Bioinformatic Analysis. J Mol Neurosci. 2019 Aug 3. doi:
10.1007/s12031-019-01355-3. [Epub ahead of print] PubMed PMID: 31377983.
)).
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To monitor the effect of CUX1 and its [[CUT domain]]s on [[APE1]] activity, DNA repair assays were performed with purified proteins and cell extracts. CUX1 protein expression was analyzed by immunohistochemistry using a tumor microarray of 150 glioblastoma samples. The effect of CUX1 knockdown and overexpression on the resistance of glioblastoma cell lines to [[temozolomide]] was investigated.

Kaur et al. showed that CUT domains stimulate APE1 activity. In agreement with these findings, CUX1 [[knockdown]] causes an increase in the number of abasic sites in genomic DNA and a decrease in APE1 activity as measured in cell extracts. Conversely, ectopic CUX1 expression increases APE1 activity and lowers the number of abasic sites. Having established that CUX1 is expressed at high levels in most glioblastomas, we next show that the resistance of glioblastoma cells to [[temozolomide]] and to a combined treatment of temozolomide and ionizing radiation is reduced following CUX1 knockdown, but increased by overexpression of CUX1 or a short protein containing only 2 CUT domains, which is active in DNA repair but devoid of transcriptional activity.

These findings indicate that CUX1 expression level impacts on the response of glioblastoma cells to treatment and identifies the CUT domains as potential therapeutic targets.
((Kaur S, Ramdzan ZM, Guiot MC, Li L, Leduy L, Ramotar D, Sabri S, Abdulkarim 
B, Nepveu A. [[CUX1]] stimulates APE1 enzymatic activity and increases the resistance
of glioblastoma cells to the mono-alkylating agent temozolomide. Neuro Oncol.
2018 Mar 27;20(4):484-493. doi: 10.1093/neuonc/nox178. PubMed PMID: 29036362;
PubMed Central PMCID: PMC5909652.)).

===== References =====