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Guanine nucleotide binding protein like-1 (GNL1) promotes cancer cell proliferation and survival through AKT/p21 CIP1 signaling cascade
- Source :
- Molecular Biology of the Cell
- Publication Year :
- 2020
- Publisher :
- The American Society for Cell Biology, 2020.
-
Abstract
- Human guanine nucleotide binding protein like 1 (GNL1) is an evolutionary conserved putative nucleolar GTPase belonging to the HSR1_MMR1 subfamily of GTPases. GNL1 was found to be highly up-regulated in various cancers. Here, we report for the first time that GNL1 inhibits apoptosis by modulating the expression of Bcl2 family of proteins and the cleavage of caspases 7 and 8. Furthermore, GNL1 protects colon cancer cells from chemo-drug-induced apoptosis. Interestingly, GNL1 up-regulates the expression of p53 and its transcriptional target, p21 but the up-regulation of p21 was found to be p53 dependent as well as independent mechanisms. Our results further demonstrate that GNL1 promotes cell growth and survival by inducing cytoplasmic retention and stabilization of p21 through AKT-mediated phosphorylation. In addition, GNL1 failed to inhibit apoptosis under p21 knockdown conditions which suggests the critical role of p21 in GNL1-mediated cell survival. Finally, an inverse correlation of GNL1, p21, and AKT expression in primary colon and breast cancer with patient survival suggests their critical role in tumorigenesis. Collectively, our study reveals that GNL1 executes its antiapoptotic function by a novel mechanism and suggests that it may function as a regulatory component of the PI3K/AKT/p21 signaling network to promote cell proliferation and survival in cancers.
- Subjects :
- Cyclin-Dependent Kinase Inhibitor p21
Cytoplasm
Cell Survival
Apoptosis
Biology
Models, Biological
03 medical and health sciences
0302 clinical medicine
GTP-Binding Proteins
Cell Line, Tumor
Neoplasms
Humans
Phosphorylation
Molecular Biology
Protein kinase B
030304 developmental biology
Cell Proliferation
0303 health sciences
Cell growth
Protein Stability
Cancer cell proliferation
Cell Biology
Articles
P21 waf1
Guanine Nucleotide Binding Protein
Cell biology
Gene Expression Regulation, Neoplastic
Cell Biology of Disease
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Tumor Suppressor Protein p53
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19394586 and 10591524
- Volume :
- 31
- Issue :
- 26
- Database :
- OpenAIRE
- Journal :
- Molecular Biology of the Cell
- Accession number :
- edsair.doi.dedup.....d27f84dd192f803a40d9886f7250bbeb