Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Galectin-3, a beta-galactoside-binding protein, is implicated in cell growth, adhesion, differentiation, and tumor progression by interactions with its ligands. Recent studies have revealed that galectin-3 suppresses apoptosis and anoikis that contribute to cell survival during metastatic cascades. Previously, it has been shown that human galectin-3 undergoes post-translational signaling modification of Ser(6) phosphorylation that acts as an "on/off" switch for its sugar-binding capability. We questioned whether galectin-3 phosphorylation is required for its anti-apoptotic function. Serine to alanine (S6A) and serine to glutamic acid (S6E) mutations were produced at the casein kinase I phosphorylation site in galectin-3. The cDNAs were transfected into a breast carcinoma cell line BT-549 that innately expresses no galectin-3. Metabolic labeling revealed that only wild type galectin-3 undergoes phosphorylation in vivo. Expression of Ser(6) mutants of galectin-3 failed to protect cells from cisplatin-induced cell death and poly(ADP-ribose) polymerase from degradation when compared with wild type galectin-3. The non-phosphorylated galectin-3 mutants failed to protect cells from anoikis with G(1) arrest when cells were cultured in suspension. In response to a loss of cell-substrate interactions, only cells expressing wild type galectin-3 down-regulated cyclin A expression and up-regulated cyclin D(1) and cyclin-dependent kinase inhibitors, i.e. p21(WAF1/CIP1) and p27(KIP1) expression levels. These results demonstrate that galectin-3 phosphorylation regulates its anti-apoptotic signaling activity.
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PMID:Galectin-3 phosphorylation is required for its anti-apoptotic function and cell cycle arrest. 1172 77

Traumatic brain injury (TBI) causes both direct and delayed tissue damage. The latter is associated with secondary biochemical changes such as cell cycle activation, which leads to neuronal death, inflammation, and glial scarring. Flavopiridol--a cyclin-dependent kinase (CDK) inhibitor that is neither specific nor selective--is neuroprotective. To examine the role of more specific CDK inhibitors as potential neuroprotective agents, we studied the effects of roscovitine in TBI. Central administration of roscovitine 30 mins after injury resulted in significantly decreased lesion volume, as well as improved motor and cognitive recovery. Roscovitine attenuated neuronal death and inhibited activation of cell cycle pathways in neurons after TBI, as indicated by attenuated cyclin G1 accumulation and phosphorylation of retinoblastoma protein. Treatment also decreased microglial activation after TBI, as reflected by reductions in ED1, galectin-3, p22(PHOX), and Iba-1 levels, and attenuated astrogliosis, as shown by decreased accumulation of glial fibrillary acidic protein. In primary cortical microglia and neuronal cultures, roscovitine and other selective CDK inhibitors attenuated neuronal cell death, as well as decreasing microglial activation and microglial-dependent neurotoxicity. These data support a multifactorial neuroprotective effect of cell cycle inhibition after TBI--likely related to inhibition of neuronal apoptosis, microglial-induced inflammation, and gliosis--and suggest that multiple CDKs are potentially involved in this process.
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PMID:Roscovitine reduces neuronal loss, glial activation, and neurologic deficits after brain trauma. 1861 15