The telomere-associated homeobox-containing protein TAH1 participates in telomere maintenance in ALT Cells

Feng, Xuyang; Luo, Zhenhua; Jiang, Shuai; Li, Feng; Han, Xin; Hu, Yang; Wang, Dan; Zhao, Yong; Ma, Wenbin; Liu, Dan; Huang, Junjiu; Songyang, Zhou

doi:10.1242/jcs.128512

Cited by 32 publications

(23 citation statements)

References 45 publications

(51 reference statements)

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“…Recently, HMBOX1 was found to bind double-stranded telomere repeats and associate with the active telomerase complex to support telomerase-dependent telomere elongation 3 . Moreover, HMBOX1 participated in telomere maintenance in alternative lengthening of telomere (ALT) cells, which extended their telomeres independent of telomerase 4 .…”

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confidence: 99%

HMBOX1 interacts with MT2A to regulate autophagy and apoptosis in vascular endothelial cells

Yue

et al. 2015

Sci Rep

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We previously found that Homeobox containing 1 (HMBOX1) was required for bone mesenchymal stem cell (BMSC) and mouse embryonic stem cell (ESC) differentiation into vascular endothelial cells (VECs). However, the function of HMBOX1 in VECs is still unknown. In this study, we found that HMBOX1 was abundantly expressed in the cytoplasm of human umbilical vascular endothelial cells (HUVECs). Knockdown of HMBOX1 induced apoptosis and inhibited autophagy. Overexpression of HMBOX1 inhibited apoptosis induced by fibroblast growth factor 2 deprivation and promoted autophagy. Metallothionein 2A (MT2A) was identified as an interaction protein with HMBOX1 by yeast two-hybrid assay, and confirmed by co-immunoprecipitation. Overexpression of HMBOX1 elevated intracellular free zinc level. Knockdown of MT2A inhibited this phenomenon. Moreover, N,N,N = ,N = -tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a zinc chelator, reversed the anti-apoptosis and pro-autophagy effects of HMBOX1. In conclusion, HMBOX1 regulated intracellular free zinc level by interacting with MT2A to inhibit apoptosis and promote autophagy in VECs.

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confidence: 99%

HMBOX1 interacts with MT2A to regulate autophagy and apoptosis in vascular endothelial cells

Yue

et al. 2015

Sci Rep

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“…Next, we investigated whether CIRP could bind directly to TERC in vitro . For this purpose, bacterially purified CIRP-GST proteins (Figure 4B ) were used in the EMSA ( 76 ). The TERC RNA probe was in vitro transcribed and radio-labeled before being incubated with the recombinant proteins.…”

Section: Resultsmentioning

confidence: 99%

Cold-inducible RNA-binding protein CIRP/hnRNP A18 regulates telomerase activity in a temperature-dependent manner

Zhang

Mao

et al. 2015

Nucleic Acids Res

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The telomerase is responsible for adding telomeric repeats to chromosomal ends and consists of the reverse transcriptase TERT and the RNA subunit TERC. The expression and activity of the telomerase are tightly regulated, and aberrant activation of the telomerase has been observed in >85% of human cancers. To better understand telomerase regulation, we performed immunoprecipitations coupled with mass spectrometry (IP-MS) and identified cold inducible RNA-binding protein (CIRP or hnRNP A18) as a telomerase-interacting factor. We have found that CIRP is necessary to maintain telomerase activities at both 32°C and 37°C. Furthermore, inhibition of CIRP by CRISPR-Cas9 or siRNA knockdown led to reduced telomerase activities and shortened telomere length, suggesting an important role of CIRP in telomere maintenance. We also provide evidence here that CIRP associates with the active telomerase complex through direct binding of TERC and regulates Cajal body localization of the telomerase. In addition, CIRP regulates the level of TERT mRNAs. At the lower temperature, TERT mRNA is upregulated in a CIRP-dependent manner to compensate for reduced telomerase activities. Taken together, these findings highlight the dual roles that CIRP plays in regulating TERT and TERC, and reveal a new class of telomerase modulators in response to hypothermia conditions.

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“…In the study using MEFs, 471 proteins were found to associate with telomeres regardless of telomere status ( 42 ). The technique QTIP utilizes SILAC coupled with mass spectrometric analysis to compare and identify quantitative differences between telomere proteins ( 34 ). A total of 258 telomere-associated proteins were identified by QTIPin HeLa cells ( 43 ).…”

Section: Construction and Contentmentioning

confidence: 99%

“…In addition, some proteins with DNA binding activities (not specific for telomere DNA sequence) can directly bind to telomere DNA. For instance, we have shown that TAH1/HMBOX1/HOT1 directly binds to telomeric double-stranded DNA and become a part of the interaction network ( 34 , 35 ).…”

Section: Introductionmentioning

confidence: 99%

TeloPIN: a database of telomeric proteins interaction network in mammalian cells

et al. 2015

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Interaction network surrounding telomeres has been intensively studied during the past two decades. However, no specific resource by integrating telomere interaction information data is currently available. To facilitate the understanding of the molecular interaction network by which telomeres are associated with biological process and diseases, we have developed TeloPIN (Telomeric Proteins Interaction Network) database (http://songyanglab.sysu.edu.cn/telopin/), a novel database that points to provide comprehensive information on protein–protein, protein–DNA and protein–RNA interaction of telomeres. TeloPIN database contains four types of interaction data, including (i) protein–protein interaction (PPI) data, (ii) telomeric proteins ChIP-seq data, (iii) telomere-associated proteins data and (iv) telomeric repeat-containing RNAs (TERRA)-interacting proteins data. By analyzing these four types of interaction data, we found that 358 and 199 proteins have more than one type of interaction information in human and mouse cells, respectively. We also developed table browser and TeloChIP genome browser to help researchers with better integrated visualization of interaction data from different studies. The current release of TeloPIN database includes 1111 PPI, eight telomeric protein ChIP-seq data sets, 1391 telomere-associated proteins and 183 TERRA-interacting proteins from 92 independent studies in mammalian cells. The interaction information provided by TeloPIN database will greatly expand our knowledge of telomeric proteins interaction network.Database URL: TeloPIN database address is http://songyanglab.sysu.edu.cn/telopin. TeloPIN database is freely available to non-commercial use.

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The telomere-associated homeobox-containing protein TAH1 participates in telomere maintenance in ALT Cells

Cited by 32 publications

References 45 publications

HMBOX1 interacts with MT2A to regulate autophagy and apoptosis in vascular endothelial cells

HMBOX1 interacts with MT2A to regulate autophagy and apoptosis in vascular endothelial cells

Cold-inducible RNA-binding protein CIRP/hnRNP A18 regulates telomerase activity in a temperature-dependent manner

TeloPIN: a database of telomeric proteins interaction network in mammalian cells

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