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Article ; Online: Cyclin-Dependent Kinases and CTD Phosphatases in Cell Cycle Transcriptional Control

Zhi-Liang Zheng

Cells, Vol 11, Iss 279, p

Conservation across Eukaryotic Kingdoms and Uniqueness to Plants

2022 Volume 279

Abstract: Cell cycle control is vital for cell proliferation in all eukaryotic organisms. The entire cell cycle can be conceptually separated into four distinct phases, Gap 1 (G1), DNA synthesis (S), G2, and mitosis (M), which progress sequentially. The precise ... ...

Abstract	Cell cycle control is vital for cell proliferation in all eukaryotic organisms. The entire cell cycle can be conceptually separated into four distinct phases, Gap 1 (G1), DNA synthesis (S), G2, and mitosis (M), which progress sequentially. The precise control of transcription, in particular, at the G1 to S and G2 to M transitions, is crucial for the synthesis of many phase-specific proteins, to ensure orderly progression throughout the cell cycle. This mini-review highlights highly conserved transcriptional regulators that are shared in budding yeast ( Saccharomyces cerevisiae ), Arabidopsis thaliana model plant, and humans, which have been separated for more than a billion years of evolution. These include structurally and/or functionally conserved regulators cyclin-dependent kinases (CDKs), RNA polymerase II C-terminal domain (CTD) phosphatases, and the classical versus shortcut models of Pol II transcriptional control. A few of CDKs and CTD phosphatases counteract to control the Pol II CTD Ser phosphorylation codes and are considered critical regulators of Pol II transcriptional process from initiation to elongation and termination. The functions of plant-unique CDKs and CTD phosphatases in relation to cell division are also briefly summarized. Future studies towards testing a cooperative transcriptional mechanism, which is proposed here and involves sequence-specific transcription factors and the shortcut model of Pol II CTD code modulation, across the three eukaryotic kingdoms will reveal how individual organisms achieve the most productive, large-scale transcription of phase-specific genes required for orderly progression throughout the entire cell cycle.
Keywords	CDK ; CTD phosphatase ; RNA polymerase II ; CTD code ; transcription ; cell cycle ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Modulation of the Pol II CTD Phosphorylation Code by Rac1 and Cdc42 Small GTPases in Cultured Human Cancer Cells and Its Implication for Developing a Synthetic-Lethal Cancer Therapy

Bo Zhang / Xuelin Zhong / Moira Sauane / Yihong Zhao / Zhi-Liang Zheng

Cells, Vol 9, Iss 3, p

2020 Volume 621

Abstract: Rho GTPases, including Rho, Cdc42, Rac and ROP subfamilies, are key signaling molecules in RNA polymerase II (Pol II) transcriptional control. Our prior work has shown that plant ROP and yeast Cdc42 GTPases similarly modulate Ser2 and Ser5 ... ...

Abstract	Rho GTPases, including Rho, Cdc42, Rac and ROP subfamilies, are key signaling molecules in RNA polymerase II (Pol II) transcriptional control. Our prior work has shown that plant ROP and yeast Cdc42 GTPases similarly modulate Ser2 and Ser5 phosphorylation status of the C-terminal domain (CTD) of the Pol II largest subunit by regulating CTD phosphatase degradation. Here, we present genetic and pharmacological evidence showing that Cdc42 and Rac1 GTPase signaling modulates a similar CTD Ser2 and Ser5 phosphorylation code in cultured human cancer cells. While siRNA knockdown of Cdc42 and Rac1 , respectively, in HeLa cells increased the level of CTD Ser phosphatases RPAP2 and FCP1, they both decreased the level of CTD kinases CDK7 and CDK13. In addition, the protein degradation inhibitor MG132 reversed the effect of THZ1, a CDK7 inhibitor which could decrease the cell number and amount of CDK7 and CDK13, accompanied by a reduction in the level of CTD Ser2 and Ser5 phosphorylation and DOCK4 and DOCK9 (the activators for Rac1 and Cdc42, respectively). Conversely, treatments of Torin1 or serum deprivation, both of which promote protein degradation, could enhance the effect of THZ1, indicating the involvement of protein degradation in controlling CDK7 and CDK13. Our results support an evolutionarily conserved signaling shortcut model linking Rho GTPases to Pol II transcription across three kingdoms, Fungi, Plantae and Animalia, and could lead to the development of a potential synthetic-lethal strategy in controlling cancer cell proliferation or death.
Keywords	rho ; rac1 ; cdc42 ; pol ii ; ctd code ; cdk7 ; dock4 ; dock9 ; thz1 ; torin1 ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Arabidopsis γ‐glutamylcyclotransferase affects glutathione content and root system architecture during sulfur starvation

Joshi, Naveen C / Andreas J. Meyer / Sajid A. K. Bangash / Thomas Leustek / Zhi‐Liang Zheng

new phytologist. 2019 Feb., v. 221, no. 3

2019

Abstract: γ‐Glutamylcyclotransferase initiates glutathione degradation to component amino acids l‐glutamate, l‐cysteine and l‐glycine. The enzyme is encoded by three genes in Arabidopsis thaliana, one of which (GGCT2;1) is transcriptionally upregulated by ... ...

Abstract	γ‐Glutamylcyclotransferase initiates glutathione degradation to component amino acids l‐glutamate, l‐cysteine and l‐glycine. The enzyme is encoded by three genes in Arabidopsis thaliana, one of which (GGCT2;1) is transcriptionally upregulated by starvation for the essential macronutrient sulfur (S). Regulation by S‐starvation suggests that GGCT2;1 mobilizes l‐cysteine from glutathione when there is insufficient sulfate for de novo l‐cysteine synthesis. The response of wild‐type seedlings to S‐starvation was compared to ggct2;1 null mutants. S‐starvation causes glutathione depletion in S‐starved wild‐type seedlings, but higher glutathione is maintained in the primary root tip than in other seedling tissues. Although GGCT2;1 is induced throughout seedlings, its expression is concentrated in the primary root tip where it activates the γ‐glutamyl cycle. S‐starved wild‐type plants also produce longer primary roots, and lateral root growth is suppressed. While glutathione is also rapidly depleted in ggct2;1 null seedlings, much higher glutathione is maintained in the primary root tip compared to the wild‐type. S‐starved ggct2;1 primary roots grow longer than the wild‐type, and lateral root growth is not suppressed. These results point to a role for GGCT2;1 in S‐starvation‐response changes to root system architecture through activity of the γ‐glutamyl cycle in the primary root tip. l‐Cysteine mobilization from glutathione is not solely a function of GGCT2;1.
Keywords	acyltransferases ; Arabidopsis thaliana ; cysteine ; gene expression regulation ; genes ; glutamic acid ; glutathione ; mutants ; root growth ; root systems ; root tips ; seedlings ; sulfates ; sulfur ; tissues ; transcription (genetics)
Language	English
Dates of publication	2019-02
Size	p. 1387-1397.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	208885-x
ISSN	1469-8137 ; 0028-646X
ISSN (online)	1469-8137
ISSN	0028-646X
DOI	10.1111/nph.15466
Database	NAL-Catalogue (AGRICOLA)

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Article: Gene coexpression network analysis of fruit transcriptomes uncovers a possible mechanistically distinct class of sugar/acid ratio-associated genes in sweet orange

Qiao, Liang / Jian Zheng / Minghao Cao / Yihong Zhao / Zhi-Liang Zheng

BMC plant biology. 2017 Dec., v. 17, no. 1

2017

Abstract: BACKGROUND: The ratio of sugars to organic acids, two of the major metabolites in fleshy fruits, has been considered the most important contributor to fruit sweetness. Although accumulation of sugars and acids have been extensively studied, whether ... ...

Abstract	BACKGROUND: The ratio of sugars to organic acids, two of the major metabolites in fleshy fruits, has been considered the most important contributor to fruit sweetness. Although accumulation of sugars and acids have been extensively studied, whether plants evolve a mechanism to maintain, sense or respond to the fruit sugar/acid ratio remains a mystery. In a prior study, we used an integrated systems biology tool to identify a group of 39 acid-associated genes from the fruit transcriptomes in four sweet orange varieties (Citrus sinensis L. Osbeck) with varying fruit acidity, Succari (acidless), Bingtang (low acid), and Newhall and Xinhui (normal acid). RESULTS: We reanalyzed the prior sweet orange fruit transcriptome data, leading to the identification of 72 genes highly correlated with the fruit sugar/acid ratio. The majority of these sugar/acid ratio-related genes are predicted to be involved in regulatory functions such as transport, signaling and transcription or encode enzymes involved in metabolism. Surprisingly, only three of these sugar/acid ratio-correlated genes are weakly correlated with sugar level and none of them overlaps with the acid-associated genes. Weighted Gene Coexpression Network Analysis (WGCNA) has revealed that these genes belong to four modules, Blue, Grey, Brown and Turquoise, with the former two modules being unique to the sugar/acid ratio control. CONCLUSION: Our results indicate that orange fruits contain a possible mechanistically distinct class of genes that may potentially be involved in maintaining fruit sugar/acid ratios and/or responding to the cellular sugar/acid ratio status. Therefore, our analysis of orange transcriptomes provides an intriguing insight into the potentially novel genetic or molecular mechanisms controlling the sugar/acid ratio in fruits.
Keywords	Citrus sinensis ; enzymes ; fruit acids ; fruits ; genes ; metabolism ; metabolites ; oranges ; organic acids and salts ; sugars ; sweetness ; transcription (genetics) ; transcriptome
Language	English
Dates of publication	2017-12
Size	p. 186.
Publishing place	BioMed Central
Document type	Article
ISSN	1471-2229
DOI	10.1186/s12870-017-1138-8
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The OSU1/QUA2/TSD2-encoded putative methyltransferase is a critical modulator of carbon and nitrogen nutrient balance response in Arabidopsis.

Peng Gao / Zeyu Xin / Zhi-Liang Zheng

PLoS ONE, Vol 3, Iss 1, p e

2008 Volume 1387

Abstract: The balance between carbon (C) and nitrogen (N) nutrients must be tightly coordinated so that cells can optimize their opportunity for metabolism, growth and development. However, the C and N nutrient balance perception and signaling mechanism remains ... ...

Abstract	The balance between carbon (C) and nitrogen (N) nutrients must be tightly coordinated so that cells can optimize their opportunity for metabolism, growth and development. However, the C and N nutrient balance perception and signaling mechanism remains poorly understood. Here, we report the isolation and characterization of two allelic oversensitive to sugar 1 mutants (osu1-1, osu1-2) in Arabidopsis thaliana. Using the cotyledon anthocyanin accumulation and root growth inhibition assays, we show that the osu1 mutants are more sensitive than wild-type to both of the imbalanced C/N conditions, high C/low N and low C/high N. However, under the balanced C/N conditions (low C/low N or high C/high N), the osu1 mutants have similar anthocyanin levels and root lengths as wild-type. Consistently, the genes encoding two MYB transcription factors (MYB75 and MYB90) and an Asn synthetase isoform (ASN1) are strongly up-regulated by the OSU1 mutation in response to high C/low N and low C/high N, respectively. Furthermore, the enhanced sensitivity of osu1-1 to high C/low N with respect to anthocyanin accumulation but not root growth inhibition can be suppressed by co-suppression of MYB75, indicating that MYB75 acts downstream of OSU1 in the high C/low N imbalance response. Map-based cloning reveals that OSU1 encodes a member of a large family of putative methyltransferases and is allelic to the recently reported QUA2/TSD2 locus identified in genetic screens for cell-adhesion-defective mutants. Accumulation of OSU1/QUA2/TSD2 transcript was not regulated by C and N balance, but the OSU1 promoter was slightly more active in the vascular system. Taken together, our results show that the OSU1/QUA2/TSD2-encoded putative methyltransferase is required for normal C/N nutrient balance response in plants.
Keywords	Medicine ; R ; Science ; Q
Subject code	580
Language	English
Publishing date	2008-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: A luciferase-based method for assay of 5′-adenylylsulfate reductase

Xiang, Xiaoli / Guangtang Pan / Thomas Leustek / Tingzhao Rong / Zhi-Liang Zheng

Analytical biochemistry. 2014 Sept. 01, v. 460

2014

Abstract: A luciferase-based method was developed for measurement of 5′-adenylylsulfate (APS) reductase (APR), an enzyme of the reductive sulfate assimilation pathway in prokaryotes and plants. APR catalyzes the two-electron reduction of APS and forms sulfite and ... ...

Abstract	A luciferase-based method was developed for measurement of 5′-adenylylsulfate (APS) reductase (APR), an enzyme of the reductive sulfate assimilation pathway in prokaryotes and plants. APR catalyzes the two-electron reduction of APS and forms sulfite and adenosine 5′-monophospahate (AMP). The luciferase-based assay measures AMP production using an enzyme-coupled system that generates luminescence. The method is shown to provide an accurate measurement of APR kinetic properties and can be used for both endpoint and continuous assays. APR activity can be measured from pure enzyme preparations as well as from crude protein extracts of tissues. In addition, the assay is ideally suited to high-throughput sample analysis of APR activity in a microtiter dish format. The method adds new capability to the study of the biochemistry and physiology of APR.
Keywords	adenosine monophosphate ; adenylyl-sulfate reductase ; catalytic activity ; crude protein ; luminescence ; physiology ; prokaryotic cells ; sulfates ; sulfites ; tissues
Language	English
Dates of publication	2014-0901
Size	p. 22-28.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1110-1
ISSN	1096-0309 ; 0003-2697
ISSN (online)	1096-0309
ISSN	0003-2697
DOI	10.1016/j.ab.2014.05.009
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A mutation in MRH2 kinesin enhances the root hair tip growth defect caused by constitutively activated ROP2 small GTPase in Arabidopsis.

Guohua Yang / Peng Gao / Hua Zhang / Shanjin Huang / Zhi-Liang Zheng

PLoS ONE, Vol 2, Iss 10, p e

2007 Volume 1074

Abstract: Root hair tip growth provides a unique model system for the study of plant cell polarity. Transgenic plants expressing constitutively active (CA) forms of ROP (Rho-of-plants) GTPases have been shown to cause the disruption of root hair polarity likely as ...

Abstract	Root hair tip growth provides a unique model system for the study of plant cell polarity. Transgenic plants expressing constitutively active (CA) forms of ROP (Rho-of-plants) GTPases have been shown to cause the disruption of root hair polarity likely as a result of the alteration of actin filaments (AF) and microtubules (MT) organization. Towards understanding the mechanism by which ROP controls the cytoskeletal organization during root hair tip growth, we have screened for CA-rop2 suppressors or enhancers using CA1-1, a transgenic line that expresses CA-rop2 and shows only mild disruption of tip growth. Here, we report the characterization of a CA-rop2 enhancer (cae1-1 CA1-1) that exhibits bulbous root hairs. The cae1-1 mutation on its own caused a waving and branching root hair phenotype. CAE1 encodes the root hair growth-related, ARM domain-containing kinesin-like protein MRH2 (and thus cae1-1 was renamed to mrh2-3). Cortical MT displayed fragmentation and random orientation in mrh2 root hairs. Consistently, the MT-stabilizing drug taxol could partially rescue the wavy root hair phenotype of mrh2-3, and the MT-depolymerizing drug Oryzalin slightly enhanced the root hair tip growth defect in CA1-1. Interestingly, the addition of the actin-depolymerizing drug Latrunculin B further enhanced the Oryzalin effect. This indicates that the cross-talk of MT and AF organization is important for the mrh2-3 CA1-1 phenotype. Although we did not observe an apparent effect of the MRH2 mutation in AF organization, we found that mrh2-3 root hair growth was more sensitive to Latrunculin B. Moreover, an ARM domain-containing MRH2 fragment could bind to the polymerized actin in vitro. Therefore, our genetic analyses, together with cell biological and pharmacological evidence, suggest that the plant-specific kinesin-related protein MRH2 is an important component that controls MT organization and is likely involved in the ROP2 GTPase-controlled coordination of AF and MT during polarized growth of root hairs.
Keywords	Medicine ; R ; Science ; Q
Subject code	580
Language	English
Publishing date	2007-10-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: OsPIE1, the rice ortholog of Arabidopsis PHOTOPERIOD-INDEPENDENT EARLY FLOWERING1, is essential for embryo development.

Yonghan Xu / Minjuan Deng / Jianfei Peng / Zhanghua Hu / Lieming Bao / Junming Wang / Zhi-Liang Zheng

PLoS ONE, Vol 5, Iss 6, p e

2010 Volume 11299

Abstract: BACKGROUND: The SWR1 complex is important for the deposition of histone variant H2A.Z into chromatin necessary to robustly regulate gene expression during growth and development. In Arabidopsis thaliana, the catalytic subunit of the SWR1-like complex, ... ...

Abstract	BACKGROUND: The SWR1 complex is important for the deposition of histone variant H2A.Z into chromatin necessary to robustly regulate gene expression during growth and development. In Arabidopsis thaliana, the catalytic subunit of the SWR1-like complex, encoded by PIE1 (PHOTOPERIOD-INDEPENDENT EARLY FLOWERING1), has been shown to function in multiple developmental processes including flowering time pathways and petal number regulation. However, the function of the PIE1 orthologs in monocots remains unknown. METHODOLOGY/FINDINGS: We report the identification of the rice (Oryza sativa) ortholog, OsPIE1. Although OsPIE1 does not exhibit a conserved exon/intron structure as Arabidopsis PIE1, its encoded protein is highly similar to PIE1, sharing 53.9% amino acid sequence identity. OsPIE1 also has a very similar expression pattern as PIE1. Furthermore, transgenic expression of OsPIE1 completely rescued both early flowering and extra petal number phenotypes of the Arabidopsis pie1-2 mutant. However, homozygous T-DNA insertional mutants of OsPIE1 in rice were embryonically lethal, in contrast to the viable mutants in the orthologous genes for yeast, Drosophila and Arabidopsis (Swr1, DOMINO and PIE1, respectively). CONCLUSIONS/SIGNIFICANCE: Taken together, our results suggest that OsPIE1 is the rice ortholog of Arabidopsis PIE1 and plays an essential role in rice embryo development.
Keywords	Medicine ; R ; Science ; Q
Subject code	580
Language	English
Publishing date	2010-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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