A Nucleosome-Free dG-dC-Rich Sequence Element Promotes Constitutive Transcription of the Essential Yeast RIO1 Gene

Angermayr, Michaela; Kerstin, Schwerdtfeger; Bandlow, Wolfhard

doi:10.1515/bc.2003.143

Cited by 8 publications

(5 citation statements)

References 38 publications

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“…It is possible that the tissue expression pattern of the RIOKs is wider than our analysis showed when the expression specific levels are very low. Indeed, both Rio1P and Rio2P are reported to be expressed at very low levels in yeast [ 6 , 33 ]. Therefore, it is possible that riok-1 and- 2 are expressed widely, but at very low levels in C. elegans and may function in rRNA processing, as is the case in other species.…”

Section: Discussionmentioning

confidence: 99%

Investigating the Role of RIO Protein Kinases in Caenorhabditis elegans

et al. 2015

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RIO protein kinases (RIOKs) are a relatively conserved family of enzymes implicated in cell cycle control and ribosomal RNA processing. Despite their functional importance, they remain a poorly understood group of kinases in multicellular organisms. Here, we show that the C. elegans genome contains one member of each of the three RIOK sub-families and that each of the genes coding for them has a unique tissue expression pattern. Our analysis showed that the gene encoding RIOK-1 (riok-1) was broadly and strongly expressed. Interestingly, the intestinal expression of riok-1 was dependent upon two putative binding sites for the oxidative and xenobiotic stress response transcription factor SKN-1. RNA interference (RNAi)-mediated knock down of riok-1 resulted in germline defects, including defects in germ line stem cell proliferation, oocyte maturation and the production of endomitotic oocytes. Taken together, our findings indicate new functions for RIOK-1 in post mitotic tissues and in reproduction.

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Section: Discussionmentioning

confidence: 99%

Investigating the Role of RIO Protein Kinases in Caenorhabditis elegans

et al. 2015

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“…Sequence profile analysis of bacterial H-NOX domains showed that they are found in predicted operons encoding genes for two component systems and diguanylate cyclases or phosphodiesterases. Furthermore, fused PAS/coiled-coil domain genes are frequently in close proximity to H-NOX genes in bacterial genomes (30). In sGC, multiple protein domains must transfer signals to each other via direct and allosteric signaling mechanism involving many regulatory interfaces.…”

Section: Discussionmentioning

confidence: 99%

Single-particle EM reveals the higher-order domain architecture of soluble guanylate cyclase

Campbell

Underbakke

Potter

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Soluble guanylate cyclase (sGC) is the primary nitric oxide (NO) receptor in mammals and a central component of the NO-signaling pathway. The NO-signaling pathways mediate diverse physiological processes, including vasodilation, neurotransmission, and myocardial functions. sGC is a heterodimer assembled from two homologous subunits, each comprised of four domains. Although crystal structures of isolated domains have been reported, no structure is available for full-length sGC. We used single-particle electron microscopy to obtain the structure of the complete sGC heterodimer and determine its higher-order domain architecture. Overall, the protein is formed of two rigid modules: the catalytic dimer and the clustered Per/Art/Sim and heme-NO/O 2 -binding domains, connected by a parallel coiled coil at two hinge points. The quaternary assembly demonstrates a very high degree of flexibility. We captured hundreds of individual conformational snapshots of free sGC, NO-bound sGC, and guanosine-5′-[(α,β)-methylene]triphosphate-bound sGC. The molecular architecture and pronounced flexibility observed provides a significant step forward in understanding the mechanism of NO signaling.N itric oxide (NO) has emerged as an integral signaling molecule in biology. Soluble guanylate cyclase (sGC), the primary receptor of NO in mammals, binds NO via an Fe II heme cofactor leading to a several hundred-fold increase in 3,5-cyclic guanosine monophosphate (cGMP) synthesis. cGMP then acts as a second messenger, targeting phosphodiesterases, ion-gated channels, and cGMP-dependent protein kinases. These target proteins go on to regulate many critical physiological functions including vasodilation, platelet aggregation, neurotransmission, and myocardial functions (1, 2). Disruptions in NO signaling have been linked to hypertension, erectile dysfunction, neurodegeneration, stroke, and heart disease (3, 4). sGC has been the focus of small-molecule modulators of activity for therapeutic advantage. Riociguat, which is a stimulator of sGC, has recently been approved for treatment of pulmonary hypertension (5). However, the mechanistic details underlying the modulation of sGC catalytic activity by NO and other small molecules remain largely unknown. Determining the structure of the full-length sGC, free and in complex with NO, is therefore a prerequisite to understanding its function and for the design and improvement of therapeutics for treatment of diseases involving the NO/cGMP pathway.The most extensively studied and physiologically relevant isoform of sGC is the 150-kDa heterodimer containing one α1 and one β1 subunit. Each subunit is comprised of four modular domains: the N-terminal heme-NO/O 2 -binding (H-NOX), the Per/Arnt/Sim (PAS), the helical, and the C-terminal catalytic domain (Fig. 1). No structure of the complete holoenzyme is available to date, and its absence precludes answering key questions such as how NO occupancy of the N-terminal β H-NOX sensor domain is communicated to the C-terminal cyclase domain. Atomic models of isola...

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“…Altogether, we believe that phosphorylation of Rio1p by CK2 has at least two biologically relevant consequences: (a) it increases Rio1 kinase activity and, conceivably, also controls interaction with other proteins (presumably during the G 1 phase); and (b) it provides a signal for commitment for degradation of Rio1p before entrance of the S phase. We have shown for the first time that the cellular concentration and activity of constitutively expressed Rio1p [15,16] are likely regulated through phosphorylation by CK2.…”

Section: Discussionmentioning

confidence: 99%

“…It is essential in yeast and is only distantly related to previously characterized protein kinases. The RIO1 gene is transcribed constitutively at an extremely low level [15,16], and Rio1p is a very low abundant protein [12]. Yeast has only one such gene, whereas at least two orthologues of Rio1p are present in higher eukaryotes.…”

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confidence: 99%

Protein kinase CK2 activates the atypical Rio1p kinase and promotes its cell‐cycle phase‐dependent degradation in yeast

et al. 2007

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The protein kinase casein kinase 2 (CK2) is ubiquitous in eukaryotes and is responsible for the Ser ⁄ Thr phosphorylation of a large number of protein substrates [1][2][3]. The active holoenzyme is most often a heterotetramer composed of two catalytic a subunits, a (encoded by CKA1) and a¢ (encoded by CKA2), and two regulatory b subunits, b and b¢ in Saccharomyces cerevisiae (CKB1 and CKB2). The enzyme occurs in all possible combinations of a and b subunits [4,5]. In yeast, deletion of the gene for one of the two catalytic subunits has little effect, but deletion of both homologous genes results in loss of viability [6]. To date, more than 300 endogenous CK2 substrates are known to be involved in quite diverse processes, e.g. cell proliferation, signal transduction, transcriptional regulation, translation and metabolism [3]. Despite this eminent role in strictly regulated cellular processes and although CK2 is indispensable for cell life, CK2 activity by itself is apparently unregulated [4,5], although some fluctuation in activity in correlation with cell-cycle progression has been seen in cultured mammalian cells [7,8]. The physiological effect of substrate phosphorylation is surprisingly low with almost all targets described to date [9,10]. In S. cerevisiae, it has been shown using temperature-sensitive CKA2 alleles that protein kinase CK2 is required for passage across the G 2 ⁄ M boundary and for cell-cycle progression through the G 1 phase [11]. Using co-immunoprecipitation combined with MS analysis, we identified the a¢ subunit of casein kinase 2 (CK2) as an interaction partner of the atypical Rio1 protein kinase in yeast. Co-purification of Rio1p with CK2 from Dcka1 or Dcka2 mutant extracts shows that Rio1p preferentially interacts with Cka2p in vitro. The C-terminal domain of Rio1p is essential and sufficient for this interaction. Six C-terminally located clustered serines were identified as the only CK2 sites present in Rio1p. Replacement of all six serine residues by aspartate, mimicking constitutive phosphorylation, stimulates Rio1p kinase activity about twofold in vitro compared with wild-type or the corresponding (S > A) 6 mutant proteins. Both mutant alleles (S > A) 6 or (S > D) 6 complement in vivo, however, growth of the RIO1 (S > A) 6 mutant is greatly retarded and shows a cell-cycle phenotype, whereas the behaviour of the RIO1 (S > D) 6 mutant is indistinguishable from wild-type. This suggests that phosphorylation by protein kinase CK2 leads to moderate activation of Rio1p in vivo and promotes cell proliferation. Physiological studies indicate that phosphorylation by CK2 renders the Rio1 protein kinase susceptible to proteolytic degradation at the G 1 ⁄ S transition in the cell-division cycle, whereas the non-phosphorylated version is resistant.Abbreviations Aky2p, adenylate kinase 2; CK2, casein kinase 2; GST, glutathione S-transferase.

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A Nucleosome-Free dG-dC-Rich Sequence Element Promotes Constitutive Transcription of the Essential Yeast RIO1 Gene

Cited by 8 publications

References 38 publications

Investigating the Role of RIO Protein Kinases in Caenorhabditis elegans

Investigating the Role of RIO Protein Kinases in Caenorhabditis elegans

Single-particle EM reveals the higher-order domain architecture of soluble guanylate cyclase

Protein kinase CK2 activates the atypical Rio1p kinase and promotes its cell‐cycle phase‐dependent degradation in yeast

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