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Kelch-like protein 38 (KLHL38)
- Target
- KLHL38
- Molecular classification
- Other (Substrate adaptor protein of Cullin 3 ubiquitin ligase complex), Ubiquitin ligase substrate-adaptor protein (part of cullin 3 RING E3 ligase complexes)
01
Overview
Kelch-like protein 38 (KLHL38) is a member of the kelch-like (KLHL) family, characterized by a BTB/POZ domain, a BACK domain, and multiple kelch repeats forming a substrate recognition interface. KLHL38 functions mainly as a substrate adaptor in cullin 3-based E3 ubiquitin ligase complexes, targeting proteins for ubiquitin-mediated degradation. Its biological roles include regulation of signaling pathways such as PI3K/AKT (through PTEN degradation), cell proliferation, migration, and autophagy. High KLHL38 expression is associated with increased tumor progression and worse prognosis in several cancers; it participates in cancer development by modulating oncogenic signaling and may also be involved in muscle differentiation through degradation of myocardin. No approved drugs currently target KLHL38 directly, but its emerging role in cancer identifies it as a novel therapeutic target and biomarker candidate.
- Other names
- C8orfK36C8ORFK36Kelch-like 38
02
Mechanism of action
Promotes ubiquitination and degradation of phosphatase and tensin homolog (PTEN), contributing to PI3K/AKT pathway activation, which drives cell proliferation and survival in tumors
03
Biological functions
Ubiquitination (targeting specific proteins for proteasomal degradation)Regulation of the Akt/PI3K signaling pathwayRegulation of autophagyPromotion of cell proliferation, migration, and invasion (especially in lung and breast cancer)
04
Disease associations
Cancer (especially lung, breast, and ovarian cancers; promotes tumorigenesis and may be prognostic marker)Heart failure (via degradation of myocardin, impacting muscle differentiation and development)
05
Safety considerations
Not explicitly reported; theoretical concerns involve possible impact on cellular homeostasis since KLHL38 modulates oncogenic pathways and basic cellular processes like protein degradation
06
Biomarkers
KLHL38 expression may serve as a prognostic biomarker in cancer, correlating with survival, tumor mutation burden, tumor stage, and immune infiltrationPotential biomarker for patient selection in lung cancers and possibly other tumor types (as high expression correlates with poor prognosis and increased tumor progression)
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