FBXO44

FBXO44 Full Name

F-box protein 44

FBXO44 Introduction

FBXO44 (F-box protein 44) is a member of the F-box protein family that acts as a substrate-recognition component of the SCF (SKP1–Cullin–F-box) E3 ubiquitin ligase complex, a central system responsible for ubiquitin-mediated proteasomal protein degradation. For researchers and drug discovery teams struggling with the challenge of controlling protein stability in complex disease pathways, FBXO44 represents a key regulatory "switch" that determines whether specific proteins are stabilized or eliminated. It recognizes target proteins through its F-box-associated structural domains and promotes K48-linked ubiquitination, the canonical signal for proteasomal degradation. One well-characterized example is its regulation of the pregnane X receptor (PXR), where FBXO44 directly binds and drives PXR ubiquitination, reducing its protein abundance and thereby influencing nuclear receptor signaling and drug metabolism-related pathways.

Beyond protein turnover, FBXO44 has gained attention as a multifunctional regulator of transcriptional control, cell cycle progression, and genome integrity. In cancer biology, where uncontrolled proliferation and transcriptional rewiring are major therapeutic challenges, FBXO44 is increasingly recognized as an oncogenic factor. In colorectal cancer, it is frequently upregulated and contributes to tumor progression by promoting degradation of the tumor suppressor FOXP1. This process enhances Cyclin E2 expression and accelerates cell cycle progression, ultimately supporting tumor growth and malignant transformation. In parallel, FBXO44 also participates in maintaining chromatin stability during DNA replication by cooperating with chromatin-modifying complexes to silence repetitive genomic elements. When FBXO44 function is disrupted, cells experience increased replication stress, DNA damage, and activation of innate immune pathways, highlighting its role in maintaining genome integrity and linking chromatin regulation with immune signaling.

Clinically, abnormal FBXO44 expression is associated with a range of human diseases, particularly cancers and age-related disorders, making it an emerging therapeutic target of interest. High FBXO44 levels are frequently correlated with poor prognosis across multiple tumor types, including breast, lung, gastric, and ovarian cancers, where it contributes to tumor growth and immune-related dysregulation. In cardiovascular disease research, FBXO44 has also been implicated in regulating cardiac aging and heart function through degradation of key signaling regulators and disruption of mitochondrial calcium homeostasis. Collectively, FBXO44 serves as a central ubiquitin ligase adaptor that integrates protein degradation, transcriptional regulation, genome stability, and stress response pathways, positioning it as a promising target for future precision therapies in cancer and degenerative diseases where proteostasis is disrupted.

Alternate Names for FBXO44

FBXO44; F-box protein 44; FBG3; FBX30; FBX6A; Fbx44; Fbxo6a; F-box only protein 44; F-box gene 3; F-box protein FBX30; F-box/G-domain protein 3;

• 1.Florke Gee RR, et al.; The F-box-only protein 44 regulates pregnane X receptor protein level by ubiquitination and degradation. Acta Pharm Sin B. 2023, 13(11):4523-4534.
  2.Nie H, et al.; FBXO44 Regulates FOXP1 Degradation Through AURKA-Dependent Phosphorylation to Promote Colorectal Cancer Progression. Adv Sci (Weinh). 2025, 12(47):e15458.