Abstract
Background: Adult T-cell leukemia (ATL) is a complex and multifaceted disease associated with human T-cell leukemia virus type I (HTLV-1) infection. Tax, the viral oncoprotein, is considered a major contributor to cell cycle deregulation in HTLV-1 transformed cells by either directly disrupting cellular factors (protein-protein interactions) or altering their transcription profile. Tax transactivates these cellular promoters by interacting with transcription factors such as CREB/ATF, NF-κB, and SRF. Therefore by examining which factors upregulate a particular set of promoters we may begin to understand how Tax orchestrates leukemia development. Results: We observed that CTLL cells stably expressing wild-type Tax (CTLL/WT) exhibited aneuploidy as compared to a Tax clone deficient for CREB transactivation (CTLL/703). To better understand the contribution of Tax transactivation through the CREB/ATF pathway to the aneuploid phenotype, we performed microarray analysis comparing CTLL/WT to CTLL/ 703 cells. Promoter analysis of altered genes revealed that a subset of these genes contain CREB/ATF consensus sequences. While these genes had diverse functions, smaller subsets of genes were found to be involved in G2/M phase regulation, in particular kinetochore assembly. Furthermore, we confirmed the presence of CREB, Tax and RNA Polymerase II at the p97Vcp and Sgtl promoters in vivo through chromatin immunoprecipitation in CTLL/WT cells. Conclusion: These results indicate that the development of aneuploidy in Tax-expressing cells may occur in response to an alteration in the transcription profile, in addition to direct protein interactions.
| Original language | English (US) |
|---|---|
| Article number | 43 |
| Journal | Retrovirology |
| Volume | 3 |
| DOIs | |
| State | Published - Jul 5 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Virology
Cite this
Involvement of HTLV-I tax and CREB in aneuploidy : A bioinformatics approach. / de la Fuente, Cynthia; Gupta, Madhur V.; Klase, Zachary; Strouss, Katharine; Cahan, Patrick; McCaffery, Timothy; Galante, Anthony; Soteropoulos, Patricia; Pumfery, Anne; Fujii, Masahiro; Kashanchi, Fatah.
In: Retrovirology, Vol. 3, 43, 05.07.2006.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Involvement of HTLV-I tax and CREB in aneuploidy
T2 - A bioinformatics approach
AU - de la Fuente, Cynthia
AU - Gupta, Madhur V.
AU - Klase, Zachary
AU - Strouss, Katharine
AU - Cahan, Patrick
AU - McCaffery, Timothy
AU - Galante, Anthony
AU - Soteropoulos, Patricia
AU - Pumfery, Anne
AU - Fujii, Masahiro
AU - Kashanchi, Fatah
PY - 2006/7/5
Y1 - 2006/7/5
N2 - Background: Adult T-cell leukemia (ATL) is a complex and multifaceted disease associated with human T-cell leukemia virus type I (HTLV-1) infection. Tax, the viral oncoprotein, is considered a major contributor to cell cycle deregulation in HTLV-1 transformed cells by either directly disrupting cellular factors (protein-protein interactions) or altering their transcription profile. Tax transactivates these cellular promoters by interacting with transcription factors such as CREB/ATF, NF-κB, and SRF. Therefore by examining which factors upregulate a particular set of promoters we may begin to understand how Tax orchestrates leukemia development. Results: We observed that CTLL cells stably expressing wild-type Tax (CTLL/WT) exhibited aneuploidy as compared to a Tax clone deficient for CREB transactivation (CTLL/703). To better understand the contribution of Tax transactivation through the CREB/ATF pathway to the aneuploid phenotype, we performed microarray analysis comparing CTLL/WT to CTLL/ 703 cells. Promoter analysis of altered genes revealed that a subset of these genes contain CREB/ATF consensus sequences. While these genes had diverse functions, smaller subsets of genes were found to be involved in G2/M phase regulation, in particular kinetochore assembly. Furthermore, we confirmed the presence of CREB, Tax and RNA Polymerase II at the p97Vcp and Sgtl promoters in vivo through chromatin immunoprecipitation in CTLL/WT cells. Conclusion: These results indicate that the development of aneuploidy in Tax-expressing cells may occur in response to an alteration in the transcription profile, in addition to direct protein interactions.
AB - Background: Adult T-cell leukemia (ATL) is a complex and multifaceted disease associated with human T-cell leukemia virus type I (HTLV-1) infection. Tax, the viral oncoprotein, is considered a major contributor to cell cycle deregulation in HTLV-1 transformed cells by either directly disrupting cellular factors (protein-protein interactions) or altering their transcription profile. Tax transactivates these cellular promoters by interacting with transcription factors such as CREB/ATF, NF-κB, and SRF. Therefore by examining which factors upregulate a particular set of promoters we may begin to understand how Tax orchestrates leukemia development. Results: We observed that CTLL cells stably expressing wild-type Tax (CTLL/WT) exhibited aneuploidy as compared to a Tax clone deficient for CREB transactivation (CTLL/703). To better understand the contribution of Tax transactivation through the CREB/ATF pathway to the aneuploid phenotype, we performed microarray analysis comparing CTLL/WT to CTLL/ 703 cells. Promoter analysis of altered genes revealed that a subset of these genes contain CREB/ATF consensus sequences. While these genes had diverse functions, smaller subsets of genes were found to be involved in G2/M phase regulation, in particular kinetochore assembly. Furthermore, we confirmed the presence of CREB, Tax and RNA Polymerase II at the p97Vcp and Sgtl promoters in vivo through chromatin immunoprecipitation in CTLL/WT cells. Conclusion: These results indicate that the development of aneuploidy in Tax-expressing cells may occur in response to an alteration in the transcription profile, in addition to direct protein interactions.
UR - http://www.scopus.com/inward/record.url?scp=33748297502&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748297502&partnerID=8YFLogxK
U2 - 10.1186/1742-4690-3-43
DO - 10.1186/1742-4690-3-43
M3 - Article
C2 - 16822311
AN - SCOPUS:33748297502
VL - 3
JO - Retrovirology
JF - Retrovirology
SN - 1742-4690
M1 - 43
ER -