Arf

Arf, often written ARF, is a term that can refer to several distinct topics in science and culture. In biology, it most commonly denotes two unrelated concepts: a family of small GTP-binding proteins called ADP-ribosylation factors, and the tumor suppressor ARF produced from the CDKN2A locus. The latter is sometimes referred to as p14ARF in humans and p19ARF in mice. In everyday language, “arf” is also an onomatopoeic representation of a dog’s bark.

ADP-ribosylation factor (ARF) refers to a family of small GTPases that regulate vesicular trafficking within cells. Mammalian genomes encode several ARF proteins, notably ARF1–ARF6, along with related ARF-like proteins (ARLs). These proteins cycle between GDP-bound inactive and GTP-bound active states and recruit coat complexes such as COPI to membranes, promoting vesicle budding and trafficking between the Golgi apparatus, endosomes, and the endoplasmic reticulum. ARF signaling also influences membrane composition and cytoskeletal organization, linking lipid metabolism to membrane trafficking. Activation is mediated by guanine nucleotide exchange factors (GEFs), and inactivation by GTPase-activating proteins (GAPs).

p14ARF/p19ARF is a tumor suppressor encoded by an alternative reading frame of the CDKN2A locus, separate from p16INK4A. ARF acts mainly by stabilizing the tumor suppressor p53: it inhibits MDM2, a negative regulator of p53, leading to cell cycle arrest or apoptosis in response to oncogenic stress. The CDKN2A locus thus encodes two distinct tumor suppressors that regulate the p53 and Rb pathways, and disruption of ARF signaling is a common feature in various cancers.

In informal usage, ar f or arf also appears as a phonetic imitation of a dog’s bark.