Cloning and Characterization of the Human USP22 Gene Promoter

Jianjun Xiong; Xiangxin Che; Xueqin Li; Huan Yu; Zhen Gong; Weidong Li
December 2012
PLoS ONE;Dec2012, Vol. 7 Issue 12, p1
Academic Journal
Ubiquitin-specific processing enzyme 22 (USP22) plays a direct role in regulating cell cycle, and its overexpression has been reported to be involved in tumor progression. However, little is known about the regulation of USP22 transcription. In this study, we cloned and characterized the human USP22 promoter. Using 59 RACE (rapid amplification of cDNA ends) analysis, the transcriptional initiation site was identified. Promoter deletion analysis showed that the sequence between -210 and 27 contains the basal promoter for USP22 in human fibroblast and tumor cells. Surprisingly, mutations in a putative Sp1 binding site immediately upstream of the USP22 transcriptional start site (-13 to -7) resulted in a significant induction of promoter activity. Further study revealed that Sp1 binds to this site in human normal fibroblast cells, and treatment with the Sp1 inhibitor mithramycin A led to a marked increase in USP22 transcript levels. Forced expression of exogenous Sp1 repressed the USP22 promoter activity in HeLa cells. In contrast, knockdown of Sp1 enhanced USP22 promoter activity and mRNA levels. These data suggest that Sp1 is a crucial regulator of USP22 transcription.


Related Articles

  • Suppression of morphological transformation by radicicol is accompanied by enhanced gelsolin expression. Kwon, Ho Jeong; Yoshida, Minoru; Nagaoka, Rie; Obinata, Takashi; Beppu, Teruhiko; Horinouchi, Sueharu // Oncogene;11/20/97, Vol. 15 Issue 21, p2625 

    Radicicol, an inhibitor of Src-family protein-tyrosine kinases, causes morphological reversion of v-src- and v-Ha-ras-transformed fibroblasts and arrest of the cell cycle at both the G1 and the G2 phases. Radicicol was found to inhibit the growth of several other oncogene-transformed cell lines...

  • Bortezomib: A New Pro-Apoptotic Agent in Cancer Treatment. Russo, A.; Bronte, G.; Fulfaro, F.; Cicero, G.; Adamo, V.; Gebbia, N.; Rizzo, S. // Current Cancer Drug Targets;Feb2010, Vol. 10 Issue 1, p55 

    Bortezomib is a proteasome inhibitor. It targets the ubiquitin-proteasome pathway with subsequent inhibition of the degradation of proteins involved in cell cycle regulation and cancer cell survival. The best known molecular mechanism concerns the inhibition of IκB breakdown and the related...

  • Therapeutic targeting of cancer cell cycle using proteasome inhibitors. Rastogi, Namrata; Mishra, Durga Prasad // Cell Division;2012, Vol. 7 Issue 1, p1 

    Proteasomes are multicatalytic protease complexes in the cell, involved in the non-lysosomal recycling of intra-cellular proteins. Proteasomes play a critical role in regulation of cell division in both normal as well as cancer cells. In cancer cells this homeostatic function is deregulated...

  • Human RAD18 Interacts with Ubiquitylated Chromatin Components and Facilitates RAD9 Recruitment to DNA Double Strand Breaks. Inagaki, Akiko; Sleddens-Linkels, Esther; van Cappellen, Wiggert A.; Hibbert, Richard G.; Sixma, Titia K.; Hoeijmakers, Jan H. J.; Grootegoed, J. Anton; Baarends, Willy M. // PLoS ONE;2011, Vol. 6 Issue 8, p1 

    RAD18 is an ubiquitin ligase involved in replicative damage bypass and DNA double-strand break (DSB) repair processes. We found that RPA is required for the dynamic pattern of RAD18 localization during the cell cycle, and for accumulation of RAD18 at sites of c-irradiation-induced DNA damage. In...

  • The BTB protein MEL-26 is a substrate-specific adaptor of the CUL-3 ubiquitin-ligase. Pintard,, Lionel; Willis, John H.; Willems, Andrew; Johnson, Jacque-Lynne F.; Sryko, Martin; Kurz, Thimo; Glaser, Sarah; Mains, Paul E.; Tyers, Mike; Bowerman, Bruce; Peter, Matthias // Nature;9/18/2003, Vol. 425 Issue 6955, p311 

    Many biological processes, such as development and cell cycle progression are tightly controlled by selective ubiquitin-dependent degradation of key substrates. In this pathway, the E3-ligase recognizes the substrate and targets it for degradation by the 26S proteasome. The SCF (Skp1-Cul1-F-box)...

  • MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. Michel, Loren S.; Liberal, Vasco; Chatterjee, Anupam; Kirchwegger, Regina; Pasche, Boris; Gerald, William; Dobles, Max; Sorger, Peter K.; Murty, V.V.V.S.; Benezra, Robert // Nature;1/18/2001, Vol. 409 Issue 6818, p355 

    Reports that the deletion of a mitotic checkpoint protein results in a defective mitotic checkpoint in both human cancer cells and murine primary embryonic fibroblasts. Complete loss of mitotic checkpoint, which results in embryonic lethality owing to chromosome mis-segregation in various...

  • A Study on the Functions of Ubiquitin Metabolic System Related Gene FBG2 in Gastric Cancer Cell Line. Zhang, Lin; Hou, Yanhong; Wang, Meng-wei; Wu, Ben-yan; Li, Nan // Internet Journal of Gastroenterology;2008, Vol. 7 Issue 2, p23 

    Objective To investigate the influence of FBG2 on the growth, proliferation, apopatosis , infiltration and cell cycle of the gastric cancer line MKN45. Methods A critical component ubiquitin-protein ligase complex FBG2 cDNA was subcloned into a constitutive vector PCDNA3.1 followed by...

  • Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. Nishitani, Hideo; Sugimoto, Nozomi; Roukos, Vassilis; Nakanishi, Yohsuke; Saijo, Masafumi; Obuse, Chikashi; Tsurimoto, Toshiki; Nakayama, Keiichi I; Nakayama, Keiko; Fujita, Masatoshi; Lygerou, Zoi; Nishimoto, Takeharu // EMBO Journal;3/8/2006, Vol. 25 Issue 5, p1126 

    Replication licensing is carefully regulated to restrict replication to once in a cell cycle. In higher eukaryotes, regulation of the licensing factor Cdt1 by proteolysis and Geminin is essential to prevent re-replication. We show here that the N-terminal 100 amino acids of human Cdt1 are...

  • APC/C regulation of axonal growth and synaptic functions in postmitotic neurons: the Liprin- $${\varvec \alpha}$$ connection. Teng, F. Y. H.; Tang, B. L. // Cellular & Molecular Life Sciences;Jul2005, Vol. 62 Issue 14, p1571 

    Protein ubiquitination has critical roles in neuronal physiology and defects in protein ubiquitination have been implicated in neurodegenerative pathology. The anaphase-promoting complex/cyclosome (APC/C) is one of two key E3 ubiquitin ligase complexes that functions in regulating cell cycle...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics