Complement component 1 Q subcomponent-binding protein (C1QBP)

Complement component 1 Q subcomponent-binding protein (C1QBP), also known as p32 or gC1qR, is a multifunctional, multicompartmental protein primarily localized in the mitochondrial matrix, but also found on the cell surface, in the nucleus, and the cytosol [4, 7, 10]. In the mitochondria, it acts as a chaperone and RNA-binding protein essential for the translation of mitochondrial-encoded proteins and the maintenance of oxidative phosphorylation (OXPHOS) [4, 7, 16]. On the cell surface, it functions as a receptor for the globular heads of C1q, as well as various viral and bacterial proteins, and components of the kinin-kallikrein system [2, 7, 14]. C1QBP is frequently overexpressed in various cancers, including breast, colon, and glioma, where it promotes tumor cell survival, migration, and metabolic adaptation to the tumor microenvironment [3, 11, 12, 16]. It also plays a critical role in infectious diseases by facilitating pathogen entry and modulating immune responses [2, 7]. Therapeutic strategies targeting C1QBP include small molecule inhibitors like M36, tumor-homing peptides such as LyP-1, and monoclonal antibodies, which aim to disrupt its oncogenic signaling and mitochondrial support [3, 11, 12, 15]. However, systemic inhibition poses risks of mitochondrial toxicity, as biallelic mutations in the C1QBP gene are linked to severe mitochondrial diseases like cardiomyopathy and progressive external ophthalmoplegia [4, 5, 9].

Other names

p32gC1qRHyaluronan-binding protein 1 (HABP1)p33Splicing factor 2-associated protein (SF2p32)GHABP1Complement C1q-binding proteinCOXPD33

Inhibition of mitochondrial oxidative phosphorylation and pro-survival signaling pathways (e.g., Akt-mTOR, MAPK) through direct binding and/or degradation of the C1QBP protein [11, 12, 15].