Table 3.

Pathogen-encoded proteins that exploit or target TRAFs to induce carcinogenesis in humans.

Pathogen proteins	TRAFs	Mechanisms	Cancer type	References
BACTERIAL ONCOPROTEINS
Cag PAI of H. pylori	TRAF1, 2, 6	Utilizes TRAF1, 2, and 6 to induce NF-κB activation and IL-8 secretion	Gastric cancer	(316, 319)
Tip-α of H. pylori	TRAF3	Induces TRAF3 protein and NF-κB activation by inhibiting miR-3178 expression, which targets TRAF3	Gastric cancer	(320)
VIRAL ONCOPROTEINS
LMP1 of EBV	TRAF1, 2, 3, 5, 6	Sequesters cellular TRAF3, and usurps TRAF1, 2, 3, 5, and 6 to mimic constitutively activated CD40 signaling, induces NF-κB1 and NF-κB2 activation, and induces	B lymphomas	(1, 172, 173, 321)
		EGFR expression	Nasopharyngeal carcinoma	(322–324)
	TRAF5, 6	Recruits TRAF5 and 6 to activate p38 and suppress the replication of EBV, maintaining the lalent state of EBV	Burkitt's lymphoma	(325)
v-FLIP of KSHV	TRAF2, 3	Recruits TRAF2 and 3 to activate NF-κB and JNK, and to induce cell survival	Primary effusion lymphoma	(326)
pUL48 of HCMV	TRAF3, 6	Deubiquitinates TRAF3 and 6 to inhibit type I IFN production, enhances cellular metabolic activity and upregulates anti-apoptotic proteins	Breast cancer, glioma	(327)
E6 protein of HPV	TRAF3	Inhibits p53 and RB expression, but E6 protein levels are inhibited by TRAF3	HNSCC	(328)
Core protein of HCV	TRAF2, 5, 6	Interacts with TRAF2, 5, and 6 to activate NF-κB and induce inflammation	Hepatocellular carcinoma	(329, 330)
Tax of HTLV-1	TRAF3, 6	Interacts with TRAF3 and 6 to induce TBK1-IKKε activation, type I IFN production and Mcl-1 stabilization	T cell leukemia	(331, 332)
VIRAL TUMOR SUPPRESSORS
E2 protein of HPV	TRAF5, 6	Interacts with TRAF5 and 6, promotes K63-linked ubiquitination of TRAF5, and potentiates TNFα-induced NF-κB activation by activating TRAF5	Cervical cancer, HNSCC	(333, 334)