ULK3

ULK3 (UNC-51-like kinase 3) is a serine/threonine protein kinase of the ULK family that functions as a regulator of Sonic Hedgehog (SHH) signaling and associated transcriptional responses mediated by GLI proteins^[1][2]. Mechanistically, ULK3 possesses kinase-dependent activity, enhances GLI1 and GLI2 transcriptional function, promotes GLI nuclear translocation, and directly phosphorylates GLI proteins, placing ULK3 as an important signaling component downstream of SHH pathway activation^[1][2]. In addition to Hedgehog signaling, ULK3 participates in cellular processes linked to autophagy, cellular senescence, and fibroblast activation, indicating a broader role in the coordination of stress-responsive signaling networks^[2]. Disease-relevant studies further show that ULK3 contributes to cancer-associated cellular phenotypes; increased ULK3 activity has been associated with fibroblast activation and tumor-promoting functions, while ULK3 has also been identified as a determinant of keratinocyte self-renewal and tumorigenesis^[2][4]. Compared with related ULK family members, ULK3 is distinguished by its strong functional connection to GLI-dependent Hedgehog signaling and by its close homology to STK36/Fused-related signaling mechanisms rather than the canonical autophagy-initiation functions commonly emphasized for ULK1 and ULK2^[1][2]. Moreover, ULK3 regulates cytokinetic abscission through phosphorylation of ESCRT-III proteins, expanding its experimental relevance beyond developmental signaling and cancer biology to fundamental studies of cell division and intracellular regulation^[3].