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Event: 924

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Activation, Sp1

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Activation, Sp1

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Cell term
epithelial cell

Organ term

Organ term
lung

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
phosphorylation	transcription factor Sp1	increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
human	Homo sapiens	High	NCBI
mouse	Mus musculus	High	NCBI
rat	Rattus norvegicus	High	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
Adult	Moderate

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Mixed	Low

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Specificity protein 1 (Sp1) is a member of the zinc finger transcription factors involved in many biological processes including cell cycle, cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. Sp1 can be phosphorylated by many kinases including PKA, PKC-zeta, ERK and CDK. Growth factors such as EGF, FGF2 and VEGF can phosphorylate Sp1 through ERK and MAPK, HGF can activate Sp1 through PI3K, MEK and PKC-zeta, and cyclin A through CDK2 (reviewed by Tan and Khachigian, 2009). There are five confirmed phosphorylation sites on Sp1: Ser59, Ser131, Thr453, Thr579, and Thr739 (Chu and Ferro, 2005). It is thought that changes in Sp1 phosphorylation status alters DNA-binding activity and hence facilitate induction or repression of gene transcription (Li et al., 2004).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

DNA binding, promoter activation, and association with other protein factors are the 3 approaches that can be pursued to confirm Sp1 activation (Chu and Ferro, 2005). Altered levels of phosphorylation reportedly result in changed DNA-binding, so examining the phosphorylation status at the known sites (Ser59, Ser131, Thr453, Thr579, and Thr739) using Western blots with phospho-specific antibodies contributes to an understanding of Sp1 acticvation. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) are DNA binding assays that can be used to assess transcription factor activity, and both have been used to interrogate Sp1 (Hewson et al., 2004). Specificity of Sp1 involvement in transcription of a given gene can be proven by inhibiting Sp1 with mithramycin A or C. This describes a very experimental approach; some protocols for e.g. DNA binding assays can be obtained via https://bio-protocol.org/. However, none of these methods is validated.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Sp1 activation has been reported in mouse, rat and human, and Sp1 is orthologous between these species.

References

List of the literature that was cited for this KE description. More help

Barbier, D., Garcia-Verdugo, I., Pothlichet, J., Khazen, R., Descamps, D., Rousseau, K., Thornton, D., Si-Tahar, M., Touqui, L., Chignard, M., et al. (2012). Influenza A Induces the Major Secreted Airway Mucin MUC5AC in a Protease–EGFR–Extracellular Regulated Kinase–Sp1–Dependent Pathway. Am. J. Respir. Cell Mol. Biol. 47, 149–157.

Chu, S., and Ferro, T.J. (2005). Sp1: Regulation of gene expression by phosphorylation. Gene 348, 1–11.

Hewson, C.A., Edbrooke, M.R., and Johnston, S.L. (2004). PMA induces the MUC5AC respiratory mucin in human bronchial epithelial cells, via PKC, EGF/TGF-α, Ras/Raf, MEK, ERK and Sp1-dependent mechanisms. J. Mol. Biol. 344, 683-695.

Li, L., He, S., Sun, J.-M., and Davie, J.R. (2004). Gene regulation by Sp1 and Sp3. Biochem. Cell Biol. 82, 460-471.

Perrais, M., Pigny, P., Copin, M.C., Aubert, J.P., and Van Seuningen, I. (2002). Induction of MUC2 and MUC5AC mucins by factors of the epidermal growth factor (EGF) family is mediated by EGF receptor/Ras/Raf/extracellular signal-regulated kinase cascade and Sp1. J. Biol. Chem. 277, 32258-32267.

Tan, N. Y., & Khachigian, L. M. (2009). Sp1 phosphorylation and its regulation of gene transcription. Mol. Cell. Biol. 29, 2483-2488.

van Seuningen, I., Pigny, P., Perrais, M., Porchet, N., and Aubert, J.-P. (2001). Transcriptional regulation of the 11p15 mucin genes. Towards new biological tools in human therapy, in inflammatory diseases and cancer? Frontiers in Bioscience 6.