MYBBP1A: a new Ipr1’s binding protein in mice

Hui, Pei; Trzciński, Krzysztof; Thompson, Claudette M.; Wu, Qiang; Kramnik, Igor

doi:10.1007/s11033-010-0042-1

Cited by 11 publications

(10 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Ipr1 protein, a member of the Sp100/Sp140 family, is strongly induced by type II interferon-γ [ 25 ], and expression of Ipr1 in mice improved their resistance to Mtb infection [ 2 ]. Additionally, Sp110 nuclear body protein, the human homologue of mouse Ipr1, plays important roles in the pathogenesis of infectious disease; Sp110 protein can facilitate the infection or replication of Anaplasma phagocytophilum and Epstein-Barr virus [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

The Arginine/Lysine-Rich Element within the DNA-Binding Domain Is Essential for Nuclear Localization and Function of the Intracellular Pathogen Resistance 1

Yao

Chen

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

The mouse intracellular pathogen resistance 1 (Ipr1) gene plays important roles in mediating host immunity and previous work showed that it enhances macrophage apoptosis upon mycobacterium infection. However, to date, little is known about the regulation pattern of Ipr1 action. Recent studies have investigated the protein-coding genes and microRNAs regulated by Ipr1 in mouse macrophages, but the structure and the functional motif of the Ipr1 protein have yet to be explored. In this study, we analyzed the domains and functional motif of the Ipr1 protein. The resulting data reveal that Ipr1 protein forms a homodimer and that the Sp100-like domain mediates the targeting of Ipr1 protein to nuclear dots (NDs). Moreover, we found that an Ipr1 mutant lacking the classic nuclear localization signal (cNLS) also translocated into the nuclei, suggesting that the cNLS is not the only factor that directs Ipr1 nuclear localization. Additionally, mechanistic studies revealed that an arginine/lysine-rich element within the DNA-binding domain (SAND domain) is critical for Ipr1 binding to the importin protein receptor NPI-1, demonstrating that this element plays an essential role in mediating the nuclear localization of Ipr1 protein. Furthermore, our results show that this arginine/lysine-rich element contributes to the transcriptional regulation and apoptotic activity of Ipr1. These findings highlight the structural foundations of Ipr1 action and provide new insights into the mechanism of Ipr1-mediated resistance to mycobacterium.

show abstract

Section: Discussionmentioning

confidence: 99%

The Arginine/Lysine-Rich Element within the DNA-Binding Domain Is Essential for Nuclear Localization and Function of the Intracellular Pathogen Resistance 1

Yao

Chen

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Furthermore, MYBBP1A and RELA, which are known to be SP110's interacting proteins and be involved in SP110's induction of macrophage apoptosis, are also studied [6,7]. Since the sub-phenotype of complex disease may usually result from interactions of multiple genetic factors, multiple methods of classification and regression tree (CART) construction and multifactor dimensionality reduction (MDR) analysis are employed to detect the effects of gene-gene interactions on the cavitary PTB.…”

Section: Introductionmentioning

confidence: 99%

The effects of SP110’s associated genes on fresh cavitary pulmonary tuberculosis in Han Chinese population

Jiang

Yue

et al. 2015

Clin Exp Med

Self Cite

View full text Add to dashboard Cite

SP110 is a promising anti-Mycobacterium tuberculosis (MTB) gene. To investigate the effects of SP110 and its associated genes, i.e., MYBBP1A and RELA, on pathological progression of MTB infection, an association study with 424 patients of fresh pulmonary tuberculosis (PTB) and 424 healthy controls was performed. Moreover, classification and regression tree and multifactor dimensionality reduction were employed to explore the effects of gene-gene interactions on cavitary PTB. The results indicated that both the heterozygous genotype GC and homozygous genotype CC in rs3809849 had significant effects on the risk of PTB (OR 1.42, 95 % CI 1.06-1.92, p 0.019; OR 1.55, 95 % CI 1.04-2.33, p = 0.033, respectively), and heterozygous genotype CT in rs9061 also had similar effects (OR 1.43, 95 % CI 1.07-1.90, p = 0.014). The rs3809849 and rs9905742 in MYBBP1A were also significantly associated with cavitary PTB (p = 0.00046 and 0.039, respectively), while rs9061 in SP110 had no such association (p = 0.06931) except its significant association with non-cavitary PTB (p = 0.0093). The interaction of MYBBP1A and RELA had significant effect on cavitary PTB (OR 4.24, 95 % CI 1.44-12.49, p = 0.005). These suggest that MYBBP1A instead of SP110 may be a genetic risk factor for cavitary PTB and play important effects on its whole progress.

show abstract

“…Approximately one-third of the global human population is infected with Mtb , making eradication of TB difficult to achieve. However, only 10% of latent infections develop into active TB, indicating that inherited factors and host immune defences can affect the outcome of Mtb infections 6 . The susceptibility to TB 1 ( sst1 ) locus on mouse chromosome 1 controls the progression of tuberculosis 7 .…”

mentioning

confidence: 99%

The Transcriptional Foundations of Sp110-mediated Macrophage (RAW264.7) Resistance to Mycobacterium tuberculosis H37Ra

Guo

Yao

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Human tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading global health problem, causing 1.3 million deaths each year. The nuclear body protein, Sp110, has been linked to TB resistance and previous work showed that it enhances macrophage apoptosis upon Mtb infection. Here, we report on the role of Sp110 in transcriptional regulation of macrophage responses to Mtb through integrated transcriptome and mechanistic studies. Transcriptome analysis revealed that Sp110 regulates genes involved in immune responses, apoptosis, defence responses, and inflammatory responses. Detailed investigation revealed that, in addition to apoptosis-related genes, Sp110 regulates cytokines, chemokines and genes that regulate intracellular survival of Mtb. Moreover, Sp110 regulates miRNA expression in macrophages, with immune and apoptosis-related miRNAs such as miR-125a, miR-146a, miR-155, miR-21a and miR-99b under Sp110 regulation. Additionally, our results showed that Sp110 upregulates BCL2 modifying factor (Bmf) by inhibiting miR-125a, and forced expression of Bmf induces macrophage apoptosis. These findings not only reveal the transcriptional basis of Sp110-mediated macrophage resistance to Mtb, but also suggest potential regulatory roles for Sp110 related to inflammatory responses, miRNA profiles, and the intracellular growth of Mtb.

show abstract

MYBBP1A: a new Ipr1’s binding protein in mice

Cited by 11 publications

References 40 publications

The Arginine/Lysine-Rich Element within the DNA-Binding Domain Is Essential for Nuclear Localization and Function of the Intracellular Pathogen Resistance 1

The Arginine/Lysine-Rich Element within the DNA-Binding Domain Is Essential for Nuclear Localization and Function of the Intracellular Pathogen Resistance 1

The effects of SP110’s associated genes on fresh cavitary pulmonary tuberculosis in Han Chinese population

The Transcriptional Foundations of Sp110-mediated Macrophage (RAW264.7) Resistance to Mycobacterium tuberculosis H37Ra

Contact Info

Product

Resources

About