About: Granzyme A Mediated Apoptosis Pathway     Goto   Sponge   Distinct   Permalink

An Entity of Type : owl:Class, within Data Space : linked.opendata.cz associated with source document(s)

AttributesValues
rdf:type
rdfs:label
  • Granzyme A Mediated Apoptosis Pathway
rdfs:subClassOf
Semantic_Type
  • Functional Concept
Preferred_Name
  • Granzyme A Mediated Apoptosis Pathway
UMLS_CUI
  • C1512273
BioCarta_ID
  • h_setPathway
ALT_DEFINITION
  • One mechanism used by cytotoxic T cells to kill tumor cells and virus-infected cells is the release of perforin and granzyme proteins. Perforin proteins form pores in the membranes of the attacked cell, allowing the entry of Granzyme A and Granzyme B. Granzyme B induces caspase activation and cleavage of factors like ICAD, releasing DFF40 to fragment DNA, one of the hallmarks of apoptotic cell death. Granzyme A is also an abundant granzyme released by cytotoxic T cells and is important in cytotoxic T cell induced apoptosis, activating caspase independent pathways. Once in a cell, Granzyme A activates DNA nicking by the recently identified DNAse NM23-H1, a tumor suppressor gene product whose expression is reduced in transformed, metastatic cells. The previous identification of NM23-H1 as a tumor suppressor indicates that its DNAse activity plays an important role in immune surveillance to prevent cancer through the induction of tumor cell apoptosis. The activation of NM23-H1 occurs indirectly, through the cleavage of proteins that inhibit NM23-H1 in the SET complex, which includes SET, Ape1, pp32 and HMG2. SET is a substrate for the Granzyme A protease, and SET cleavage relieves NM23-H1 inhibition to cause apoptotic DNA degradation. In addition to inhibiting NM23-H1, SET has nucleosome assembly activity and also may help the interaction of transcriptional regulation with chromatin structure by interacting with the transcriptional coactivator CBP. The targets of Granzyme A found in the SET complex also have other important functions. Ape1 repairs oxidative DNA damage, reduces transcription factors involved in immediate early responses, and its cleavage by Granzyme A may contribute to DNA degradation and apoptosis. HMG2 is an acidic chromatin-associated protein that bends DNA, alters chromatin structure and alters the accessibility of genes for transcription. In addition to acting as a nucleosome assembly factor and an inhibitor of NM23-H1, SET inhibits DNA and histone methylation by the CBP transcriptional coactivator. The tumor suppressor pp32 is not cleaved by Granzyme A but is part of the SET complex. Other targets of Granzyme A include nuclear lamins responsible for maintaining nuclear structure and histones, the basic building blocks of chromatin structure. The common involvement of the proteins of the SET complex in chromatin structure and DNA repair suggest that they work together to protect chromatin and DNA structure and that inactivation of the complex contributes to apoptosis by blocking the maintenance of DNA and chromatin structural integrity.BIOCARTA
Legacy_Concept_Name
  • Granzyme_A_Mediated_Apoptosis_Pathway
FULL_SYN
  • Granzyme A mediated Apoptosis PathwayPTBIOCARTA
  • Granzyme A Mediated Apoptosis PathwayPTNCI
code
  • C39230
is someValuesFrom of
Faceted Search & Find service v1.16.118 as of Jun 21 2024


Alternative Linked Data Documents: ODE     Content Formats:   [cxml] [csv]     RDF   [text] [turtle] [ld+json] [rdf+json] [rdf+xml]     ODATA   [atom+xml] [odata+json]     Microdata   [microdata+json] [html]    About   
This material is Open Knowledge   W3C Semantic Web Technology [RDF Data] Valid XHTML + RDFa
OpenLink Virtuoso version 07.20.3240 as of Jun 21 2024, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (126 GB total memory, 46 GB memory in use)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software