PATZ1 Is a DNA Damage-Responsive Transcription Factor That Inhibits p53 Function

Date

2015-05-01

Author

Keskin, Nazli
Deniz, Emre
Eryilmaz, Jitka
Un, Manolya
Batur, Tugce
Ersahin, Tulin
Atalay, Rengül
Sakaguchi, Shinya
Ellmeier, Wilfried
ERMAN, MEHMET BATU

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

206
views

0
downloads

Insults to cellular health cause p53 protein accumulation, and loss of p53 function leads to tumorigenesis. Thus, p53 has to be tightly controlled. Here we report that the BTB/POZ domain transcription factor PATZ1 (MAZR), previously known for its transcriptional suppressor functions in T lymphocytes, is a crucial regulator of p53. The novel role of PATZ1 as an inhibitor of the p53 protein marks its gene as a proto-oncogene. PATZ1-deficient cells have reduced proliferative capacity, which we assessed by transcriptome sequencing (RNA-Seq) and real-time cell growth rate analysis. PATZ1 modifies the expression of p53 target genes associated with cell proliferation gene ontology terms. Moreover, PATZ1 regulates several genes involved in cellular adhesion and morphogenesis. Significantly, treatment with the DNA damage-inducing drug doxorubicin results in the loss of the PATZ1 transcription factor as p53 accumulates. We find that PATZ1 binds to p53 and inhibits p53-dependent transcription activation. We examine the mechanism of this functional inhibitory interaction and demonstrate that PATZ1 excludes p53 from DNA binding. This study documents PATZ1 as a novel player in the p53 pathway.

Subject Keywords

Finger protein mazr, Helper-free, High-titer, At-hook, Gene, Domain, Methylation, Recognition, Expression, 53bp1

URI

https://hdl.handle.net/11511/30740

Journal

MOLECULAR AND CELLULAR BIOLOGY

DOI

https://doi.org/10.1128/mcb.01475-14

Collections

Graduate School of Informatics, Article

Suggestions

OpenMETU
Core

SMN loss dysregulates microtubule-associated proteins in spinal muscular atrophy model Zobaroğlu Özer, Pelin; Koyunoğlu, Dila; Son, Çağdaş Devrim; Erdem-Yurter, Hayat Erdem; BORA, GAMZE (2022-05-01) © 2022 Elsevier Inc.Spinal muscular atrophy (SMA) is a rare neurodegenerative disease caused by the absence of survival motor neuron (SMN) protein. SMN loss results in impairments of the cytoskeleton, including microtubules and regulatory proteins. However, the contribution of microtubule-associated proteins (MAPs) to microtubule dysregulations in SMA is not fully understood. In this study, we investigated neuronal MAPs responsible for the microtubule stability and growth, including MAP1A, MAP2, MAP6, MAP7,...
Gene expressions of Mn-SOD and GPx-1 in streptozotocin-induced diabetes: effect of antioxidants Sadi, Goekhan; Güray, Nülüfer Tülün (Springer Science and Business Media LLC, 2009-07-01) Increased oxidative stress and impaired antioxidant defense mechanisms are believed to be the important factors contributing to the pathogenesis and progression of diabetes mellitus. In this study, we have reported the effects of the streptozotocin-induced diabetes on the gene expression and the activities of two antioxidant enzymes, manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx). We also studied the effects of two antioxidants, vitamin C and DL-alpha-lipoic acid (LA), on the system...
RNA-biology ruling cancer progression? Focus on 3 ' UTRs and splicing Erson Bensan, Ayşe Elif (Springer Science and Business Media LLC, 2020-09-01) The protein-coding regions of mRNAs have the information to make proteins and hence have been at the center of attention for understanding altered protein functions in disease states, including cancer. Indeed, the discovery of genomic alterations and driver mutations that change protein levels and/or activity has been pivotal in our understanding of cancer biology. However, to better understand complex molecular mechanisms that are deregulated in cancers, we also need to look at non-coding parts of mRNAs, i...
EGF-SNX3-EGFR axis drives tumor progression and metastasis in triple-negative breast cancers. Cicek, Esra; Circir, Ayca; Oyken, Merve; Akbulut Caliskan, Ozge; Dioken, Didem Naz; Guntekin Ergun, Sezen; Cetin-Atalay, Rengul; Sapmaz, Aysegul; Ovaa, Huib; Sahin, Ozgur; Erson Bensan, Ayşe Elif (2021-10-30) Epidermal growth factor receptor (EGFR) has critical roles in epithelial cell physiology. Over-expression and over-activation of EGFR have been implicated in diverse cancers, including triple-negative breast cancers (TNBCs), prompting anti‐EGFR therapies. Therefore, developing potent therapies and addressing the inevitable drug resistance mechanisms necessitates deciphering of EGFR related networks. Here, we describe Sorting Nexin 3 (SNX3), a member of the recycling retromer complex, as a critical player in...
MTA-1 expression is associated with metastasis and epithelial to mesenchymal transition in colorectal cancer cells Cagatay, Seda Tuncay; Cimen, Ismail; SAVAŞ, BERNA; Banerjee, Sreeparna (Springer Science and Business Media LLC, 2013-04-01) Although metastasis associated protein 1 (MTA1) has been widely linked to tumor metastasis, the relevant mechanisms remain to be elucidated, especially in colorectal cancer (CRC). Here, we have investigated the link between MTA1, metastasis and epithelial-mesenchymal transition (EMT) in CRC. Eighteen normal colon tissues and 91 resected tumor samples were analyzed for MTA1 expression by immunohistochemistry (IHC). IHC indicated low or no nuclear MTA1 expression in the normal tissues and significantly higher...

Citation Formats

N. Keskin et al., “PATZ1 Is a DNA Damage-Responsive Transcription Factor That Inhibits p53 Function,” MOLECULAR AND CELLULAR BIOLOGY, pp. 1741–1753, 2015, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/30740.