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On the function of the interferon-inducible p53 target gene TRIM22

Petersson, Jessica LU (2011) In Lund Unviersity, Faculty of Medicine Doctoral Dissertation Series 2011:101.
Abstract
The interferon-inducible p53-target gene TRIM22 (Staf50) is a member of the TRIM (TRIpartite Motif) family. The TRIM family is a family of RING (Really Interesting New Gene) proteins, defined through a tripartite motif, containing a RING-domain, one or two B-boxes and a Coiled-coil-domain. The TRIM proteins are involved in diverse biological functions, such as apoptosis, cell-cycle- progression and viral defence. Interferons (IFNs) are pleiotropic cytokines with antiviral, anti-proliferative, proapoptotic and immunmodulatory functions. Similar to TRIM22, many TRIM proteins are upregulated in response to IFNs, and many are involved in defence towards viruses, including TRIM22. TRIM22 has been shown to restrict HIV-1, hepatitis B and... (More)
The interferon-inducible p53-target gene TRIM22 (Staf50) is a member of the TRIM (TRIpartite Motif) family. The TRIM family is a family of RING (Really Interesting New Gene) proteins, defined through a tripartite motif, containing a RING-domain, one or two B-boxes and a Coiled-coil-domain. The TRIM proteins are involved in diverse biological functions, such as apoptosis, cell-cycle- progression and viral defence. Interferons (IFNs) are pleiotropic cytokines with antiviral, anti-proliferative, proapoptotic and immunmodulatory functions. Similar to TRIM22, many TRIM proteins are upregulated in response to IFNs, and many are involved in defence towards viruses, including TRIM22. TRIM22 has been shown to restrict HIV-1, hepatitis B and encephalomyocarditis virus. p53 is probably one of the most important tumour suppressor genes, and is positioned in the centre of signalling pathways that prevent proliferation and survival of potentially malignant cells. So far only TRIM22 and TRIM19 (PML) have been shown to be upregulated in response to p53, but recently several TRIM proteins have been shown to interact with and regulate p53.



In my thesis, I have characterised the subcellular localisation and the functions of TRIM22. In paper I I show that endogenous TRIM22 localises to both the nucleus and cytoplasm. Furthermore, TRIM22 colocalises with the centrosomes irrespective of cell-cycle-phase, and with the endoplasmatic reticulum in primary cells and in cell-lines. In paper II I show that overexpressed TRIM22 suppresses translation through direct or indirect interaction with the translation initiation factor eIF4E and disruption of the eIF4F-complex. My data suggest that TRIM22 may suppress translation of a subset of mRNAs, particularly dependent on eIF4F for their translation. In paper III I show overexpressed TRIM22 to induce either repressed proliferation or cell-death depending on cellular context. Taken together, my data show cell-death-inducing, antiproliferative, translation-inhibitory effects of TRIM22, consistent with a role both as a tumour suppressor downstream of p53-signalling, and with immunomodulation downstream of IFNs. However, many new questions have been raised and further studies are warranted to understand all aspects of the function of TRIM22. (Less)
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author
supervisor
opponent
  • Professor Jönsson, Jan-Ingvar, Linköping university
organization
publishing date
type
Thesis
publication status
published
subject
keywords
TRIM22, Staf50, p53, IFN, translation, proliferation, cell death
in
Lund Unviersity, Faculty of Medicine Doctoral Dissertation Series
volume
2011:101
pages
110 pages
publisher
Division of Haematology and Transfusion Medicine
defense location
Segerfalksalen, BMC, Sölvegatan 17, Lund
defense date
2011-12-02 09:00
ISSN
1652-8220
ISBN
978-91-86871-51-2
language
English
LU publication?
yes
id
7d51549a-b12c-4add-a7dc-b4b6001b336f (old id 2203221)
date added to LUP
2011-11-16 10:05:56
date last changed
2016-09-19 08:44:47
@phdthesis{7d51549a-b12c-4add-a7dc-b4b6001b336f,
  abstract     = {The interferon-inducible p53-target gene TRIM22 (Staf50) is a member of the TRIM (TRIpartite Motif) family. The TRIM family is a family of RING (Really Interesting New Gene) proteins, defined through a tripartite motif, containing a RING-domain, one or two B-boxes and a Coiled-coil-domain. The TRIM proteins are involved in diverse biological functions, such as apoptosis, cell-cycle- progression and viral defence. Interferons (IFNs) are pleiotropic cytokines with antiviral, anti-proliferative, proapoptotic and immunmodulatory functions. Similar to TRIM22, many TRIM proteins are upregulated in response to IFNs, and many are involved in defence towards viruses, including TRIM22. TRIM22 has been shown to restrict HIV-1, hepatitis B and encephalomyocarditis virus. p53 is probably one of the most important tumour suppressor genes, and is positioned in the centre of signalling pathways that prevent proliferation and survival of potentially malignant cells. So far only TRIM22 and TRIM19 (PML) have been shown to be upregulated in response to p53, but recently several TRIM proteins have been shown to interact with and regulate p53. <br/><br>
<br/><br>
In my thesis, I have characterised the subcellular localisation and the functions of TRIM22. In paper I I show that endogenous TRIM22 localises to both the nucleus and cytoplasm. Furthermore, TRIM22 colocalises with the centrosomes irrespective of cell-cycle-phase, and with the endoplasmatic reticulum in primary cells and in cell-lines. In paper II I show that overexpressed TRIM22 suppresses translation through direct or indirect interaction with the translation initiation factor eIF4E and disruption of the eIF4F-complex. My data suggest that TRIM22 may suppress translation of a subset of mRNAs, particularly dependent on eIF4F for their translation. In paper III I show overexpressed TRIM22 to induce either repressed proliferation or cell-death depending on cellular context. Taken together, my data show cell-death-inducing, antiproliferative, translation-inhibitory effects of TRIM22, consistent with a role both as a tumour suppressor downstream of p53-signalling, and with immunomodulation downstream of IFNs. However, many new questions have been raised and further studies are warranted to understand all aspects of the function of TRIM22.},
  author       = {Petersson, Jessica},
  isbn         = {978-91-86871-51-2},
  issn         = {1652-8220},
  keyword      = {TRIM22,Staf50,p53,IFN,translation,proliferation,cell death},
  language     = {eng},
  pages        = {110},
  publisher    = {Division of Haematology and Transfusion Medicine},
  school       = {Lund University},
  series       = {Lund Unviersity, Faculty of Medicine Doctoral Dissertation Series},
  title        = {On the function of the interferon-inducible p53 target gene TRIM22},
  volume       = {2011:101},
  year         = {2011},
}