Human DNA-binding peptidyl-prolyl cis/trans isomerase Par14 is cell cycle dependently expressed and associates with chromatin in vivo

Saningong, Akuma Divine; Bayer, Peter

doi:10.1186/s12858-015-0033-x

Cited by 9 publications

(13 citation statements)

References 41 publications

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“…Knockdown of cellular Par14 levels results in a decrease in the ribosome processing rate (68). In this case, the localization of Par14 appears to be due to association with nuclophosmin B23 or direct binding to DNA (68,70). Collectively, it appears that several prolyl isomerases are recruited to RNA-containing complexes, and this suggests that cis-trans prolyl isomerization of RNA proximal proteins is critical for their dynamic functions.…”

Section: Discussionmentioning

confidence: 95%

The basic tilted helix bundle domain of the prolyl isomerase FKBP25 is a novel double-stranded RNA binding module

Dilworth¹,

Upadhyay²,

Bonnafous³

et al. 2017

Nucleic Acids Research

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Prolyl isomerases are defined by a catalytic domain that facilitates the cis–trans interconversion of proline residues. In most cases, additional domains in these enzymes add important biological function, including recruitment to a set of protein substrates. Here, we report that the N-terminal basic tilted helix bundle (BTHB) domain of the human prolyl isomerase FKBP25 confers specific binding to double-stranded RNA (dsRNA). This binding is selective over DNA as well as single-stranded oligonucleotides. We find that FKBP25 RNA-association is required for its nucleolar localization and for the vast majority of its protein interactions, including those with 60S pre-ribosome and early ribosome biogenesis factors. An independent mobility of the BTHB and FKBP catalytic domains supports a model by which the N-terminus of FKBP25 is anchored to regions of dsRNA, whereas the FKBP domain is free to interact with neighboring proteins. Apart from the identification of the BTHB as a new dsRNA-binding module, this domain adds to the growing list of auxiliary functions used by prolyl isomerases to define their primary cellular targets.

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Section: Discussionmentioning

confidence: 95%

The basic tilted helix bundle domain of the prolyl isomerase FKBP25 is a novel double-stranded RNA binding module

Dilworth¹,

Upadhyay²,

Bonnafous³

et al. 2017

Nucleic Acids Research

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“…2A) (19,21). The overlapping cellular functions of Par14 and Par17 include chro-matin remodeling, cell cycle progression, rRNA processing, and tubulin polymerization (22)(23)(24).…”

mentioning

confidence: 99%

Parvulin 14 and Parvulin 17 Bind to HBx and cccDNA and Upregulate Hepatitis B Virus Replication from cccDNA to Virion in an HBx-Dependent Manner

Saeed

Kim

Piracha

et al. 2019

J Virol

160

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The parvulin 14 (Par14) and parvulin 17 (Par17) proteins, which are both encoded by the PIN4 gene, play roles in protein folding, chromatin remodeling, DNA binding, ribosome biogenesis, and cell cycle progression. However, the effects of Par14 and Par17 on viral replication have never been explored. In this study, we found that, in the presence of HBx, either Par14 or Par17 could upregulate hepatitis B virus (HBV) replication, whereas in the absence of HBx, neither Par14 nor Par17 had any effect on replication. Overexpression of Par14/Par17 markedly increased the formation of covalently closed circular DNA (cccDNA), synthesis of HBV RNA and DNA, and virion secretion. Conversely, PIN4 knockdown significantly decreased HBV replication in HBV-transfected and -infected cells. Coimmunoprecipitation revealed that Par14/Par17 engaged in direct physical interactions with HBx in the cytoplasm, nucleus, and mitochondria, possibly mediated through substrate-binding residues on Par14/Par17 (E46/D74 and E71/D99, respectively) and conserved 19R20P-28R29P motifs on HBx. Furthermore, these interactions enhanced HBx stability, promoted HBx translocation to the nuclear and mitochondrial fractions, and increased HBV replication. Chromatin immunoprecipitation assays revealed that, in the presence of HBx, Par14/Par17 were efficiently recruited to cccDNA and promoted transcriptional activation via specific DNA-binding residues (S19/44). In contrast, in the absence of HBx, Par14/Par17 bound cccDNA only at the basal level and did not promote transcriptional activation. Taken together, our results demonstrate that Par14 and Par17 upregulate HBV RNA transcription and DNA synthesis, thereby increasing the HBV cccDNA level, through formation of the cccDNA-Par14/17-HBx complex. IMPORTANCE The HBx protein plays an essential regulatory role in HBV replication. We found that substrate-binding residues on the human parvulin peptidylprolyl cis/trans isomerase proteins Par14 and Par17 bound to conserved arginine-proline (RP) motifs on HBx in the cytoplasm, nucleus, and mitochondria. The HBx-Par14/Par17 interaction stabilized HBx; promoted its translocation to the nucleus and mitochondria; and stimulated multiple steps of HBV replication, including cccDNA formation, HBV RNA and DNA synthesis, and virion secretion. In addition, in the presence of HBx, the Par14 and Par17 proteins bound to cccDNA and promoted its transcriptional activation. Our results suggest that inhibition or knockdown of Par14 and Par17 may represent a novel therapeutic option against HBV infection.

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“…Knockdown of Par14 mRNA decelerates the processing of pre-rRNA to 18 and 28 S rRNA, demonstrating an essential role of the protein in ribosome biogenesis (Fujiyama-Nakamura et al, 2009). Although ribosome biogenesis is mainly assigned to the G1 phase of the cell cycle (Donati et al, 2012), Par14 expression is enhanced in the S as well as in the G2/M phase (Saningong and Bayer, 2015) suggesting a more pronounced function in DNAreplication, DNA repair and/or chromatin remodeling. The nuclear export of Par14 requires phosphorylation of Ser 7 and Ser 9 by the PKB/Akt kinase (or PKC) and is maintained by 14-3-3 protein in a Crm1 dependent way (Reimer, 2003).…”

Section: The Cellular Function Of Hpar14 Is Regulated By Ptmmentioning

confidence: 99%

“…Whereas a Ser Glu phosphate mimic mutant does not only restore this function, but even shifts the cytoplasmic/nuclear ratio of the protein to a complete nuclear location . In the nucleus dephosphorylated Par14 associates with chromatin (Saningong and Bayer, 2015) and co-localizes to B23 in the nucleolus (Fujiyama-Nakamura et al, 2009), where it associates to pre-ribosomal ribonuclear protein (pre-rRNP) complexes (Fujiyama et al, 2002;Fujiyama-Nakamura et al, 2009). The interaction of Par14 with these complexes as well as its activity depend on the presence of the unstructured N-terminal extension.…”

Section: The Cellular Function Of Hpar14 Is Regulated By Ptmmentioning

confidence: 99%

“…Par14/17 Reference Targets in G2/M phase and S-phase Highest expression in G2/M phase and S-phase (Saningong and Bayer, 2015;Lu et al, 1996) IRS-1 dependent signaling IRS-1 dependent signaling (Zhang et al, 2013a;Nakatsu et al, 2009;Nakatsu et al, 2010a) Splicing of RNA Involved in RNA processing (Xu et al, 2003;Fujiyama-Nakamura et al, 2009) Tubulin stabilization Tubulin polymerization (Lu et al, 1999b;Thiele et al, 2011) Located in nuclear speckles Located in nucleolus (Par14) (Rippmann et al, 2000;Fujiyama-Nakamura et al, 2009) Interaction with CK2…”

Section: Pin1mentioning

confidence: 99%

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Structure and function of the human parvulins Pin1 and Par14/17

Matena

Rehic

Hönig

et al. 2018

Biological Chemistry

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Parvulins belong to the family of peptidyl-prolyl cis/trans isomerases (PPIases) assisting in protein folding and in regulating the function of a broad variety of proteins in all branches of life. The human representatives Pin1 and Par14/17 are directly involved in processes influencing cellular maintenance and cell fate decisions such as cell-cycle progression, metabolic pathways and ribosome biogenesis. This review on human parvulins summarizes the current knowledge of these enzymes and intends to oppose the well-studied Pin1 to its less wellexamined homolog human Par14/17 with respect to structure, catalytic and cellular function.

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Human DNA-binding peptidyl-prolyl cis/trans isomerase Par14 is cell cycle dependently expressed and associates with chromatin in vivo

Cited by 9 publications

References 41 publications

The basic tilted helix bundle domain of the prolyl isomerase FKBP25 is a novel double-stranded RNA binding module

The basic tilted helix bundle domain of the prolyl isomerase FKBP25 is a novel double-stranded RNA binding module

Parvulin 14 and Parvulin 17 Bind to HBx and cccDNA and Upregulate Hepatitis B Virus Replication from cccDNA to Virion in an HBx-Dependent Manner

Structure and function of the human parvulins Pin1 and Par14/17

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