LDOC1L Human

Leucine Zipper, Down-Regulated in Cancer 1 (LDOC1) is a gene that encodes a protein with a leucine zipper-like motif and an SH3-binding domain. This protein is involved in regulating intracellular signal transduction and gene transcription . LDOC1 has been identified as a low-expressed gene in several tumor cells, making it a significant focus of cancer research .

The LDOC1 gene was first identified in 1999 by Nagasaki et al., who found that it was down-regulated in various cancer cells . The protein encoded by LDOC1 has a calculated molecular mass of approximately 17 kDa and contains a leucine zipper-like motif in its N-terminal region and a proline-rich region similar to an SH3-binding domain .

LDOC1 plays a crucial role in modulating cell proliferation, apoptosis, and migration. It has been shown to interact with Guanine nucleotide-binding protein-like 3-like (GNL3L) to modulate Nuclear Factor-kappa B (NF-κB) signaling during cell proliferation . The interaction between LDOC1 and GNL3L destabilizes endogenous GNL3L levels and downregulates GNL3L-induced cell proliferation .

LDOC1 is considered a tumor suppressor gene. Its expression is significantly lower in tumor tissues compared to normal tissues . The down-regulation of LDOC1 has been associated with poor prognosis in various cancers, including hepatocellular carcinoma (HCC) . Overexpression of LDOC1 in HCC cell lines has been shown to decrease cell proliferation, colony formation, and migration, while increasing apoptosis . This suggests that LDOC1 may serve as a favorable prognostic biomarker in cancer .

The tumor-suppressive functions of LDOC1 are believed to be mediated through the inhibition of the AKT/mTOR pathway . Overexpression of LDOC1 reduces the phosphorylated levels of AKT and mTOR, leading to the inactivation of this pathway . Additionally, LDOC1 has been shown to interact with NF-κB subunit p65, reversing the effects of GNL3L on NF-κB-dependent transcriptional activity .