What does MDA5 do?

MDA5 (melanoma differentiation-associated protein 5) is a RIG-I-like receptor dsRNA helicase enzyme that is encoded by the IFIH1 gene in humans. MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and functions as a pattern recognition receptor capable of detecting viruses.

What does MDA5 recognize?

MDA5 recognizes nucleic acids associated with viral infections such as dsRNAs and has two amino-terminal caspase recruitment domains (CARDs).

What are the structures that RIG-I and MDA5 recognize?

RIG-I and MDA5 recognize a complementary set of cytosolic viral dsRNA ligands. Their activation is tightly regulated by phosphorylation, ubiquitination, and host proteins such as LGP2.

How are RIG-I and MDA5 signaling pathways activated?

Figure 1. RIG-I/MDA5 signaling pathway RIG-I and MDA5 are first activated by recognition of PAMP dsRNA, which causes them to interact with MAVS.

How does MDA5 interact with mitochondrial antiviral signalling proteins?

Activated MDA5 interacts with the mitochondrial antiviral signalling proteins ( MAVS) through its caspase activation and recruitment domains (CARDs) at the N-terminus. The MAVS then work as a multiprotein complex to recruit the inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKε) along with the serine/threonine-protein kinase 1 (TBK1).

What is the function of MDA5 in melanoma?

MDA5 (melanoma differentiation-associated protein 5) is a RIG-I-like receptor dsRNA helicase enzyme that in humans is encoded by the IFIH1 gene. MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and functions as a pattern recognition receptor (recognizing dsRNA) that is a sensor for viruses.

How are RIG-I and MDA5 related to NF-κB?

RIG-I and MDA5 also activate the NF-κB pathway. RIG-I appears to act upstream of the canonical pathway, which results in the translocation of the two functional NF-κB units (p50 and p65) into the nucleus, while MDA5 appears to affect NF-κB expression independently from this pathway.