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The telomere-associated homeobox-containing protein TAH1/HMBOX1 participates in telomere maintenance in ALT cells.
J Cell Sci 2013; 126(Pt 17):3982-9JC

Abstract

The majority of cancer cells rely on elevated telomerase expression and activity for rapid growth and proliferation. Telomerase-negative cancer cells, by contrast, often employ the alternative lengthening of telomeres (ALT) pathway to maintain telomeres. ALT cells are characterized by long and dynamic telomeres and the presence of ALT-associated promyelocytic leukemia (PML) bodies (APBs). Previous work has shown the importance of APBs to the ALT pathway, but their formation and precise role remain unclear. Here, we demonstrate that a homeobox-containing protein known as HMBOX1 can directly bind telomeric double-stranded DNA and associate with PML nuclear bodies. Hence, we renamed this protein TAH1 for telomere-associated homeobox-containing protein 1. TAH1 knockdown significantly reduced the number of APBs and led to an increase in DNA damage response signals at telomeres. Importantly, TAH1 inhibition also notably reduced the presence of telomere C-circles, indicating altered ALT activity. Our findings point to TAH1 as a novel link between pathways that regulate DNA damage responses, PML nuclear bodies, and telomere homeostasis in ALT cells, and provide insight into how ALT cells may achieve sustained growth and proliferation independent of the telomerase.

Authors+Show Affiliations

Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23813958

Citation

Feng, Xuyang, et al. "The Telomere-associated Homeobox-containing Protein TAH1/HMBOX1 Participates in Telomere Maintenance in ALT Cells." Journal of Cell Science, vol. 126, no. Pt 17, 2013, pp. 3982-9.
Feng X, Luo Z, Jiang S, et al. The telomere-associated homeobox-containing protein TAH1/HMBOX1 participates in telomere maintenance in ALT cells. J Cell Sci. 2013;126(Pt 17):3982-9.
Feng, X., Luo, Z., Jiang, S., Li, F., Han, X., Hu, Y., ... Songyang, Z. (2013). The telomere-associated homeobox-containing protein TAH1/HMBOX1 participates in telomere maintenance in ALT cells. Journal of Cell Science, 126(Pt 17), pp. 3982-9. doi:10.1242/jcs.128512.
Feng X, et al. The Telomere-associated Homeobox-containing Protein TAH1/HMBOX1 Participates in Telomere Maintenance in ALT Cells. J Cell Sci. 2013 Sep 1;126(Pt 17):3982-9. PubMed PMID: 23813958.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The telomere-associated homeobox-containing protein TAH1/HMBOX1 participates in telomere maintenance in ALT cells. AU - Feng,Xuyang, AU - Luo,Zhenhua, AU - Jiang,Shuai, AU - Li,Feng, AU - Han,Xin, AU - Hu,Yang, AU - Wang,Dan, AU - Zhao,Yong, AU - Ma,Wenbin, AU - Liu,Dan, AU - Huang,Junjiu, AU - Songyang,Zhou, Y1 - 2013/06/26/ PY - 2013/7/2/entrez PY - 2013/7/3/pubmed PY - 2014/4/26/medline KW - ALT pathway KW - Alternative lengthening of telomeres KW - DNA damage response KW - HMBOX1 KW - Homeobox KW - TAH1 KW - Telomere SP - 3982 EP - 9 JF - Journal of cell science JO - J. Cell. Sci. VL - 126 IS - Pt 17 N2 - The majority of cancer cells rely on elevated telomerase expression and activity for rapid growth and proliferation. Telomerase-negative cancer cells, by contrast, often employ the alternative lengthening of telomeres (ALT) pathway to maintain telomeres. ALT cells are characterized by long and dynamic telomeres and the presence of ALT-associated promyelocytic leukemia (PML) bodies (APBs). Previous work has shown the importance of APBs to the ALT pathway, but their formation and precise role remain unclear. Here, we demonstrate that a homeobox-containing protein known as HMBOX1 can directly bind telomeric double-stranded DNA and associate with PML nuclear bodies. Hence, we renamed this protein TAH1 for telomere-associated homeobox-containing protein 1. TAH1 knockdown significantly reduced the number of APBs and led to an increase in DNA damage response signals at telomeres. Importantly, TAH1 inhibition also notably reduced the presence of telomere C-circles, indicating altered ALT activity. Our findings point to TAH1 as a novel link between pathways that regulate DNA damage responses, PML nuclear bodies, and telomere homeostasis in ALT cells, and provide insight into how ALT cells may achieve sustained growth and proliferation independent of the telomerase. SN - 1477-9137 UR - https://www.unboundmedicine.com/medline/citation/23813958/The_telomere_associated_homeobox_containing_protein_TAH1/HMBOX1_participates_in_telomere_maintenance_in_ALT_cells_ L2 - http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=23813958 DB - PRIME DP - Unbound Medicine ER -