The main function of the A kinase-anchoring proteins (AKAPs) is to target the cyclic AMP-dependent protein kinase A (PKA) to its cellular substrates through the interaction with its regulatory subunits. Besides anchoring of PKA, AKAP8 participates in regulating the histone H3 lysine 4 (H3K4) histone methyltransferase (HMT) complexes. It is also involved in DNA replication, apoptosis, transcriptional silencing of rRNA genes, alternative splicing, and chromatin condensation during mitosis. In this study, we focused on the interaction between AKAP8 and the core subunit of all known H3K4 HMT complexes-DPY30 protein. Here, we demonstrate that the PKA-binding domain of AKAP8 and the C-terminal domain of DPY30, also called Dpy-30 motif, are crucial for the interaction between these proteins. We show that a single amino acid substitution in DPY30 L69D affects its dimerization and completely abolishes its interaction with AKAP8 and another DPY30-binding partner brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1), which is also AKAP domain-containing protein. We further demonstrate that AKAP8 interacts with DPY30 and the RII alpha regulatory subunit of PKA both in the interphase and in mitotic cells, and we show evidences that AKAP8L, a homologue of AKAP8, interacts with core subunits of the H3K4 HMT complexes, which suggests its role as a potential regulator of these complexes. The results presented here reinforce the analogy between AKAP8-RII alpha and AKAP8-DPY30 interactions, postulated before, and improve our understanding of the complexity of the cellular functions of the AKAP8 protein.Abbreviations AKAP8, A-kinase anchoring protein 8; AKAP8L, A-kinase anchoring protein 8 like; ASH2L, absent, small, or homeotic 2-like protein; BAP18, BPTF-associated protein of 18 kDa; BIG1, brefeldin A-inhibited guanine nucleotide-exchange protein; co-IP, co-immunoprecipitation; DBM, DPY30-binding motif; GST, glutathione S-transferase; H3K4, histone H3 lysine 4; HDAC3, histone deacetylase 3; HEK293, human embryonic kidney 293 cell line; His-tag, polyhistidine-tag; HMT, histone methyltransferase; Kif2A, kinesin family member 2A; KMT, histone lysine methyltransferase; MLL, mixed lineage leukemia; PI, propidium iodide; PKA, cAMP-dependent protein kinase; PRKAR2a, protein kinase cAMP-dependent type II regulatory subunit alpha; RbBP5, retinoblastoma-binding protein 5; RIIa, cAMP-dependent protein kinase type IIalpha regulatory subunit; SAC, spindle assembly checkpoint; TAP tag, tandem affinity purification tag; TPR, translocated promoter region protein; WB, Western blot; WDR5, WD repeat domain 5; WRAD, WDR5-RbBP5-ASH2L-DPY30 complex.

Human papillomaviruses (HPVs) are considered to be key etiological agents responsible for the induction and development of cervical cancer. However, it has been suggested that HPV infection alone may not be sufficient to promote cervical carcinogenesis, and other unknown factors might be required to establish the disease. One of the suggested proteins whose deregulation has been linked with oncogenesis is transcription factor Yin Yang 1 (YY1). YY1 is a multifunctional protein that is involved not only in the regulation of gene transcription and protein modification, but can also control important cell signaling pathways, such as cell growth, development, differentiation, and apoptosis. Vital functions of YY1 also indicate that the protein could be involved in tumorigenesis. The overexpression of this protein has been observed in different tumors, and its level has been correlated with poor prognoses of many types of cancers. YY1 can also regulate the transcription of viral genes. It has been documented that YY1 can bind to the HPV long control region and regulate the expression of viral oncogenes E6 and E7; however, its role in the HPV life cycle and cervical cancer development is different. In this review, we explore the role of YY1 in regulating the expression of cellular and viral genes and subsequently investigate how these changes inadvertently contribute toward the development of cervical malignancy.

Wirusy onkogenne (onkowirusy) są zaangażowane w powstawanie około 12% nowotworów u ludzi. Obecnie wirusy, o których wiadomo, że powodują raka, to wirusy zapalenia wątroby typu C i B (HCV i HBV), wirusy brodawczaka ludzkiego (HPV), wirus polyoma komórek Merkla (MCV), ludzki herpeswirus-8 (HHV-8) i ludzki wirus limfotropowy komórek T (HTLV-1). Wirusy nie są jednak pełnymi kancerogenami i w procesie transformacji nowotworowej odgrywają różną rolę. Onkowirusy mogą bezpośrednio zakłócać funkcjonowanie genów kodujących komórkowe białka regulatorowe w wyniku insercji własnego genomu do genomu komórkowego. Mają także własne geny kodujące białka, które zaburzają regulację procesów komórkowych lub zawierają onkogeny wirusowe v-onc, które mogą brać udział bezpośrednio w rozwoju procesu nowotworowego.

Wirusy są wewnątrzkomórkowymi patogenami, które wykorzystują liczne procesy komórkowe oraz białka i czynniki wirusowe do swojej replikacji. Obecnie nie ma odpowiednich środków umożliwiających zwalczanie licznych zakażeń wirusowych. Skuteczny lek przeciwwirusowy nie powinien uszkadzać komórkowych procesów metabolicznych w zakażonej komórce, jak również w komórkach niezainfekowanych. Rośliny stanowią potencjalne źródło czynników przeciwwirusowych, takich jak: alkaloidy, flawonoidy, kwasy fenolowe, fenylopropanoidy, ligniny, terpenoidy, chininy, taniny, tiofeny, poliacetyleny czy białka. Niektóre z tych czynników wykazują szerokie spektrum aktywności przeciwwirusowej.

BackgroundBacteriophages from the Bastillevirinae subfamily have proven effective against bacteria from the Bacillus genus including organisms from B. cereus group which causes food poisoning and persistent contamination of industrial installations. However, successful application of these phages in biocontrol depends on understanding of their biology and stability in different environments.MethodsIn this study we isolated a novel virus from the garden soil in Wrocław (Poland) and named it Thurquoise. Genome of the phage was sequenced using Illumina technology and assembled as a single continuous contig that represents consensus result of different assembly algorithms. Its morphology was determined using Cryo-EM imaging while the dynamics of replication by turbidimetric lysis assay. We also determined phage host range in the efficiency of plating (EOP) assay. Finally, the stability of the Thurquoise was tested by long term incubation in buffers containing different ions (Mg2+, Ca2+, Mn2+, Zn2+, Cu2+, K+, Co2+, Fe3+, Cs+) and freezing with various cryoprotectants (glycerol, gelatin, saccharose, trehalose).ResultsWe present a complete, carefully annotated genome of the Thurquoise phage with 226 identified protein genes and 18 tRNAs. The complex virion structure of this phage is typical for the Bastillevirinae family. Confirmed hosts include selected bacteria from the Bacillus cereus group - specifically B. thuringiensis and B. mycoides. Latent and eclipse periods of Thurquoise in the isolation host last ~40 min and ~50 min respectively. The phage remains viable for more than 8 weeks in variants of SM buffer with magnesium, calcium, cesium, manganese or potassium and can withstand numerous freeze-thaw cycles if protected by the addition of 15% glycerol or, to a lesser extent, 2% gelatin.ConclusionThe Thurquoise phage is the exemplar of the new candidate species in Caruleovirus genus in the Bastillevirinae subfamily of the Herelleviridae family with genome, morphology and biology typical for these taxa.With proper buffer formulation, this virus (and likely related phages) can be safely stored in common freezers and refrigerators for a considerable time.