PMID- 36011046
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220830
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 16
DP  - 2022 Aug 22
TI  - TNF Receptor Associated Factor 2 (TRAF2) Signaling in Cancer.
LID - 10.3390/cancers14164055 [doi]
LID - 4055
AB  - Tumor necrosis factor (TNF) receptor associated factor-2 (TRAF2) has been 
      originally identified as a protein interacting with TNF receptor 2 (TNFR2) but 
      also binds to several other receptors of the TNF receptor superfamily (TNFRSF). 
      TRAF2, often in concert with other members of the TRAF protein family, is 
      involved in the activation of the classical NFkappaB pathway and the stimulation of 
      various mitogen-activated protein (MAP) kinase cascades by TNFRSF receptors 
      (TNFRs), but is also required to inhibit the alternative NFkappaB pathway. TRAF2 has 
      also been implicated in endoplasmic reticulum (ER) stress signaling, the 
      regulation of autophagy, and the control of cell death programs. TRAF2 fulfills 
      its functions by acting as a scaffold, bringing together the E3 ligase cellular 
      inhibitor of apoptosis-1 (cIAP1) and cIAP2 with their substrates and various 
      regulatory proteins, e.g., deubiquitinases. Furthermore, TRAF2 can act as an E3 
      ligase by help of its N-terminal really interesting new gene (RING) domain. The 
      finding that TRAF2 (but also several other members of the TRAF family) interacts 
      with the latent membrane protein 1 (LMP1) oncogene of the Epstein-Barr virus 
      (EBV) indicated early on that TRAF2 could play a role in the oncogenesis of 
      B-cell malignancies and EBV-associated non-keratinizing nasopharyngeal carcinoma 
      (NPC). TRAF2 can also act as an oncogene in solid tumors, e.g., in colon cancer 
      by promoting Wnt/beta-catenin signaling. Moreover, tumor cell-expressed TRAF2 has 
      been identified as a major factor-limiting cancer cell killing by cytotoxic 
      T-cells after immune checkpoint blockade. However, TRAF2 can also be 
      context-dependent as a tumor suppressor, presumably by virtue of its inhibitory 
      effect on the alternative NFkappaB pathway. For example, inactivating mutations of 
      TRAF2 have been associated with tumor development, e.g., in multiple myeloma and 
      mantle cell lymphoma. In this review, we summarize the various TRAF2-related 
      signaling pathways and their relevance for the oncogenic and tumor suppressive 
      activities of TRAF2. Particularly, we discuss currently emerging concepts to 
      target TRAF2 for therapeutic purposes.
FAU - Siegmund, Daniela
AU  - Siegmund D
AD  - Division of Molecular Internal Medicine, Department of Internal Medicine II, 
      University Hospital Wurzburg, 97080 Wurzburg, Germany.
FAU - Wagner, Jennifer
AU  - Wagner J
AD  - Division of Molecular Internal Medicine, Department of Internal Medicine II, 
      University Hospital Wurzburg, 97080 Wurzburg, Germany.
FAU - Wajant, Harald
AU  - Wajant H
AUID- ORCID: 0000-0002-2005-3949
AD  - Division of Molecular Internal Medicine, Department of Internal Medicine II, 
      University Hospital Wurzburg, 97080 Wurzburg, Germany.
LA  - eng
GR  - Si 1128/6-1/Deutsche Forschungsgemeinschaft/
GR  - 70114009/German Cancer Aid/
PT  - Journal Article
PT  - Review
DEP - 20220822
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9406534
OTO - NOTNLM
OT  - B-cell lymphoma
OT  - TNF receptor associated factor 2 (TRAF2)
OT  - apoptosis
OT  - autophagy
OT  - cellular inhibitor of apoptosis 1/2 (cIAP1/2)
OT  - necroptosis
OT  - nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFkappaB)
OT  - tumor necrosis factor (TNF)
COIS- The authors declare that they have no conflict of interest.
EDAT- 2022/08/27 06:00
MHDA- 2022/08/27 06:01
PMCR- 2022/08/22
CRDT- 2022/08/26 01:14
PHST- 2022/07/07 00:00 [received]
PHST- 2022/08/05 00:00 [revised]
PHST- 2022/08/19 00:00 [accepted]
PHST- 2022/08/26 01:14 [entrez]
PHST- 2022/08/27 06:00 [pubmed]
PHST- 2022/08/27 06:01 [medline]
PHST- 2022/08/22 00:00 [pmc-release]
AID - cancers14164055 [pii]
AID - cancers-14-04055 [pii]
AID - 10.3390/cancers14164055 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 Aug 22;14(16):4055. doi: 10.3390/cancers14164055.