RB1CC1

RB1CC1 stands for RB1-inducible coiled-coil 1 and is a human gene that encodes a large cytoplasmic scaffold protein also known as FIP200. It is a core component of the ULK1 complex, which initiates autophagy in mammalian cells. Because of its RB1-responsive expression, RB1CC1 was identified as a gene induced by the retinoblastoma tumor suppressor pathway.

As part of the ULK1 complex, RB1CC1 acts as a structural scaffold that coordinates the assembly of autophagy factors at sites of autophagosome formation. It directly interacts with ULK1 (or ULK2) and ATG13 and relies on extensive coiled-coil regions to mediate protein–protein interactions. This positioning enables the initiation of autophagy in response to cellular cues such as nutrient scarcity or energy stress.

Regulation of RB1CC1 activity is tied to the broader control of autophagy by the nutrient-sensing pathways. The ULK1 complex is inhibited by mTORC1 under nutrient-rich conditions and activated by AMPK during energy stress, leading to autophagy induction in which RB1CC1 participates as a central scaffold.

In humans and other vertebrates, RB1CC1/FIP200 is a large, conserved protein of about 200 kDa. Its proper function is essential for autophagy, and alterations in RB1CC1 expression or activity have been discussed in the context of cancer biology, neurodegenerative disease, and immune responses, reflecting the diverse roles of autophagy in health and disease.

Genetic disruption of RB1CC1 in model systems impairs autophagy and can disrupt development, underscoring its critical role in cellular homeostasis.