Dynein light chain rp3 acts as a nuclear matrix-associated transcriptional modulator in a dynein-independent pathway

Yeh, Ting‐Yu; Chuang, Jen-Zen; Sung, Ching-Hwa

doi:10.1242/jcs.02472

Cited by 21 publications

(11 citation statements)

References 68 publications

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“…This analysis revealed matches with dynlt1/3 dynein light chains (DLCs) of D. melanogaster and C. reinhardtii strongly suggesting that MGG_01005 is the M. oryzae orthologue. Cytoplasmic dynein is a microtubule-based complex involved in a variety of cellular activities 23 – 25 . It comprises two heavy chains (DHCs) and two or three intermediate chains (DICs), light intermediate chains (DLICs) as well as DLCs 26 – 29 .…”

Section: Discussionmentioning

confidence: 99%

Structure based function-annotation of hypothetical protein MGG_01005 from Magnaporthe oryzae reveals it is the dynein light chain orthologue of dynlt1/3

Huang

Yang

et al. 2018

Sci Rep

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Magnaporthe oryzae is a model fungal plant pathogen employed for studying plant-fungi interactions. Whole genome sequencing and bioinformatics analyses revealed that this fungal pathogen has more than 12,000 protein-coding genes with 65% of the genes remaining functionally un-annotated. Here, we determine the structure of the hypothetical protein, MGG_01005 and show that it is the Magnaporthe oryzae Dynein light chain Tctex-type 1 (dynlt1/3), demonstrated by its structural similarity to other orthologous dynlt1 proteins and its conserved interaction with the N-terminus of the Magnaporthe oryzae dynein intermediate chain, MoDyn1I2. In addition, we present the structure of the MGG_01005-MoDyn1I2 complex together with mutagenesis studies that reveals a di-histidine motif interaction with a glutamate residue in the dynein intermediate chain within a conserved molecular interface. These results demonstrate the utility of structure-based annotation and validate it as a viable approach for the molecular assignment of hypothetic proteins from phyto-pathogenic fungi.

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Section: Discussionmentioning

confidence: 99%

Structure based function-annotation of hypothetical protein MGG_01005 from Magnaporthe oryzae reveals it is the dynein light chain orthologue of dynlt1/3

Huang

Yang

et al. 2018

Sci Rep

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“…Interestingly, the distribution of L2 in the dynein light-chain knockdown cells strongly resembles the Golgi-localized L2 and pseudogenome described in this study. Intriguingly, the dynein light-chain rp3, which shares 55% homology with Tctex1, has been shown to associate with the nuclear matrix, where a subset localized to ND10 (53). Tctex1 has also been found in interphase nuclei (54).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Role for the trans -Golgi Network in Human Papillomavirus 16 Pseudovirus Infection

Day

Thompson

Schowalter

et al. 2013

J Virol

129

175

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Human papillomavirus 16 (HPV16) enters its host cells by a process that most closely resembles macropinocytosis. Uncoating occurs during passage through the endosomal compartment, and the low pH encountered in this environment is essential for infection. Furin cleavage of the minor capsid protein, L2, and cyclophilin B-mediated separation of L2 and the viral genome from the major capsid protein, L1, are necessary for escape from the late endosome (LE). Following this exodus, L2 and the genome are found colocalized at the ND10 nuclear subdomain, which is essential for efficient pseudogenome expression. However, the route by which L2 and the genome traverse the intervening cytoplasm between these two subcellular compartments has not been determined. This study extends our understanding of this phase in PV entry in demonstrating the involvement of the Golgi complex. With confocal microscopic analyses involving 5-ethynyl-2=-deoxyuridine (EdU)-labeled pseudogenomes and antibodies to virion and cellular proteins, we found that the viral pseudogenome and L2 travel to the trans-Golgi network (TGN) following exit from the LE, while L1 is retained. This transit is dependent upon furin cleavage of L2 and can be prevented pharmacologically with either brefeldin A or golgicide A, inhibitors of anterograde and retrograde Golgi trafficking. Additionally, Rab9a and Rab7b were determined to be mediators of this transit, as expression of dominant negative versions of these proteins, but not Rab7a, significantly inhibited HPV16 pseudovirus infection. P apillomaviruses (PV) comprise a large family of nonenveloped viruses that infect epithelial sites in many species. The high-risk human papillomaviruses (HPV) are the causative agents of some common malignancies, most notably cervical cancer. The virus capsid, which encloses the 8-kb double-stranded circular DNA genome, is composed of 72 pentamers of the major capsid protein L1 and up to 72 copies of L2, the minor capsid protein. The L1 protein possesses the ability to self-assemble in the absence of L2. In the virion, each molecule of L2 is associated with an L1 pentamer, but it is largely buried within the intact, mature virus capsid and exerts its influence largely after the entry and uncoating process, rather than during initial host engagement (1).Elucidation of the infectious entry by PV has been established mainly through the in vitro study of HPV pseudovirions, which are composed of L1-L2 capsids surrounding a reporter plasmid. These particles, structurally indistinguishable from native virions, are considered to be relevant tools to study PV infection and entry (2). Following the initial interaction of HPV pseudovirions with the host cell (in vitro) or the basement membrane (in vivo), a conformational change in the capsid leads to exposure of the N terminus of L2, which allows access of furin to a consensus furin/ proprotein convertase site at the N terminus that is conserved across all known L2 species (3). This cleavage is necessary for infectious entry of the virus, altho...

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“…DYNLT1 also interacts with Lfc, a guanine nucleotide exchange factor in a phosphorylation dependent manner to regulate neurogenesis [69], [70]. RP3, a dynein light chain subunit, localizes to the nucleus and is involved in transcriptional regulation [71]. Localization studies showed a sub-population of DYNLT1 in the nucleus [63].…”

Section: Discussionmentioning

confidence: 99%

Dynein Light Chain 1 (DYNLT1) Interacts with Normal and Oncogenic Nucleoporins

Sarma

Yaseen

2013

PLoS ONE

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The chimeric oncoprotein NUP98-HOXA9 results from the t(7;11)(p15;p15) chromosomal translocation and is associated with acute myeloid leukemia. It causes aberrant gene regulation and leukemic transformation through mechanisms that are not fully understood. NUP98-HOXA9 consists of an N-terminal portion of the nucleoporin NUP98 that contains many FG repeats fused to the DNA-binding homeodomain of HOXA9. We used a Cytotrap yeast two-hybrid assay to identify proteins that interact with NUP98-HOXA9. We identified Dynein Light Chain 1 (DYNLT1), an integral 14 KDa protein subunit of the large microtubule-based cytoplasmic dynein complex, as an interaction partner of NUP98-HOXA9. Binding was confirmed by in vitro pull down and co-immunoprecipitation assays and the FG repeat region of NUP98-HOXA9 was shown to be essential for the interaction. RNAi-mediated knockdown of DYNLT1 resulted in reduction of the ability of NUP98-HOXA9 to activate transcription and also inhibited the ability of NUP98-HOXA9 to induce proliferation of primary human hematopoietic CD34+ cells. DYNLT1 also showed a strong interaction with wild-type NUP98 and other nucleoporins containing FG repeats. Immunofluorescence analysis showed that DYNLT1 localizes primarily to the nuclear periphery, where it co-localizes with the nuclear pore complex, and to the cytoplasm. Deletion studies showed that the interactions of the nucleoporins with DYNLT1 are dependent predominantly on the C-terminal half of the DYNLT1. These data show for the first time that DYNLT1 interacts with nucleoporins and plays a role in the dysregulation of gene expression and induction of hematopoietic cell proliferation by the leukemogenic nucleoporin fusion, NUP98-HOXA9.

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Dynein light chain rp3 acts as a nuclear matrix-associated transcriptional modulator in a dynein-independent pathway

Cited by 21 publications

References 68 publications

Structure based function-annotation of hypothetical protein MGG_01005 from Magnaporthe oryzae reveals it is the dynein light chain orthologue of dynlt1/3

Structure based function-annotation of hypothetical protein MGG_01005 from Magnaporthe oryzae reveals it is the dynein light chain orthologue of dynlt1/3

Identification of a Role for the trans -Golgi Network in Human Papillomavirus 16 Pseudovirus Infection

Dynein Light Chain 1 (DYNLT1) Interacts with Normal and Oncogenic Nucleoporins

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