Detection of an Appropriate Kinase Activity in Branchial Arches I and II That Coincides with Peak Expression of the Treacher Collins Syndrome Gene Product, Treacle

Jones, Natalie Carmaline; Farlie, Peter G.; Minichiello, J.; Newgreen, Don

doi:10.1093/hmg/8.12.2239

Cited by 30 publications

(22 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous experiments have shown that the association between NBS1 and many of its interactors, such as MDC1 and CtIP, is mediated by NBS1's FHA domain, which binds to protein motifs phosphorylated by CK2 (14-16). TCOF1 harbors 10 highly repetitive regions, known as treacle repeats, containing conserved CK2 sites and is a known CK2 substrate (17,18). Consistent with these observations, we identified a CK2 subunit CSNK2B as part of a TCOF1 complex (Fig.…”

Section: Nbs1 Localization To Nucleoli After Ir Is Dependent On Caseisupporting

confidence: 85%

Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response

Ciccia

Huang

Izhar

et al. 2014

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

120

View full text Add to dashboard Cite

The signal transduction pathway of the DNA damage response (DDR) is activated to maintain genomic integrity following DNA damage. The DDR promotes genomic integrity by regulating a large network of cellular activities that range from DNA replication and repair to transcription, RNA splicing, and metabolism. In this study we define an interaction between the DDR factor NBS1 and TCOF1, a nucleolar protein that regulates ribosomal DNA (rDNA) transcription and is mutated in Treacher Collins syndrome. We show that NBS1 relocalizes to nucleoli after DNA damage in a manner dependent on TCOF1 and on casein kinase II and ATM, which are known to modify TCOF1 by phosphorylation. Moreover, we identify a putative ATM phosphorylation site that is required for NBS1 relocalization to nucleoli in response to DNA damage. Last, we report that TCOF1 promotes cellular resistance to DNA damaging agents. Collectively, our findings identify TCOF1 as a DDR factor that could cooperate with ATM and NBS1 to suppress inappropriate rDNA transcription and maintain genomic integrity after DNA damage.T he faithful conservation of genomic information is an essential process for cell survival and for preventing malignant transformation (1). To maintain genomic integrity, DNA has to be protected from damage either spontaneously induced or generated by environmental sources, including ionizing radiation or chemical agents. The DNA damage response (DDR) is a signal transduction network that is activated to maintain genomic integrity after DNA damage (1, 2). A principal component of the DDR is the ATM kinase, which is primarily activated by the presence of DNA double-strand breaks (DSBs).DSBs are deleterious DNA lesions that can lead to cell death if unresolved. DSBs are fixed either by joining the two DNA ends together by nonhomologous end joining (NHEJ) or by homologydirected repair mediated by homologous recombination (HR) (3). The regulation of DSB end-processing represents a key step in the choice between NHEJ and HR. Whereas NHEJ occurs with minimal end-processing, extensive resection of DNA ends and formation of single-stranded DNA regions is required for the initiation of HR (4, 5).NBS1 is a critical component of the heterotrimeric MRE11-RAD50-NBS1 (MRN) complex, which plays a central role in the repair of DSBs through the activation of the DDR and the initiation of HR. After binding and stabilizing DSB ends, the MRN complex recruits ATM and the mediator protein MDC1 to the break site through their direct interaction with NBS1. MDC1 subsequently associates with the phosphorylated histone variant H2AX (γH2AX) locally to amplify the ATM signaling cascade at DSBs (6-9). Direct interaction with NBS1 also promotes the recruitment of the DNA repair factor CtIP to DSB ends by the MRN complex, where it promotes end resection to initiate HR (10). The importance of NBS1 to the maintenance of genomic integrity is further highlighted by the predisposition to growth defects, craniofacial abnormalities, and B-cell lymphomas of patients with Nijmegen breaka...

show abstract

Section: Nbs1 Localization To Nucleoli After Ir Is Dependent On Caseisupporting

confidence: 85%

Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response

Ciccia

Huang

Izhar

et al. 2014

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

120

View full text Add to dashboard Cite

show abstract

“…They share a characteristic sequence rich in serines and acidic amino acids forming phosphorylation sites for CK2 [100] close to a stretch of basic amino acids. Nucleolin, Srp40p, Nopp140, and TCOF1 are nucleolar proteins and known substrates for CK2 [101][102][103][104]. Nucleolin and Nopp140 can be highly phosphorylated, and the phosphorylation process of Nopp140 by CK2 occurs in a cooperative manner with phospho-serines produced by CK2, creating new CK2 phosphorylation sites [103].…”

Section: Protein Pyrophosphorylationmentioning

confidence: 99%

Inositol pyrophosphates: structure, enzymology and function

Barker

Illies

Gaboardi

et al. 2009

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

The stereochemistry of the inositol backbone provides a platform on which to generate a vast array of distinct molecular motifs that are used to convey information both in signal transduction and many other critical areas of cell biology. Diphosphoinositol phosphates, or inositol pyrophosphates, are the most recently characterized members of the inositide family. They represent a new frontier with both novel targets within the cell and novel modes of action. This includes the proposed pyrophosphorylation of a unique subset of proteins. We review recent insights into the structures of these molecules and the properties of the enzymes which regulate their concentration. These enzymes also act independently of their catalytic activity via protein-protein interactions. This unique combination of enzymes and products has an important role in diverse cellular processes including vesicle trafficking, endo- and exocytosis, apoptosis, telomere length regulation, chromatin hyperrecombination, the response to osmotic stress, and elements of nucleolar function.

show abstract

“…A kinase activity in avian branchial arches, thought to be CK2, phosphorylates the protein treacle, the product of the TCOF1 gene that is mutated in Treacher Collins syndrome (TCS). TCS is a craniofacial disorder that affects the embryonic branchial arches leading to face abnormalities [ 87 ].…”

Section: Ck2 In Pharyngeal Arch Derivativesmentioning

confidence: 99%

CK2 in Organ Development, Physiology, and Homeostasis

Ortega

Prince-Wright

Domı́nguez

2015

Protein Kinase CK2 Cellular Function in Normal and Disease States

View full text Add to dashboard Cite

The serine/threonine kinase CK2 is associated with a wide variety of cellular processes, including cell growth, cell proliferation, and cell apoptosis. These cellular processes are vital for proper cell function, organogenesis, embryogenesis, and organ homeostasis. Indeed, CK2 is essential for embryonic development in different model organisms; however, the cellular, biochemical, molecular, and signaling mechanisms that CK2 utilizes to control embryo development are poorly defi ned. In this chapter, we review the effect of CK2α knockout in the developing organs and review the literature to understand the role of CK2α in organ formation. Published studies show roles for CK2 in the control of embryonic organ development, as well as a role for CK2α in organ homeostasis and physiology. In addition, CK2 also plays a role in a number of organ diseases.

show abstract

Detection of an Appropriate Kinase Activity in Branchial Arches I and II That Coincides with Peak Expression of the Treacher Collins Syndrome Gene Product, Treacle

Cited by 30 publications

References 18 publications

Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response

Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response

Inositol pyrophosphates: structure, enzymology and function

CK2 in Organ Development, Physiology, and Homeostasis

Contact Info

Product

Resources

About