Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : email@example.com
|Ref Type||Journal Article|
|Authors||Gong L, Govan JM, Evans EB, Dai H, Wang E, Lee SW, Lin HK, Lazar AJ, Mills GB, Lin SY|
|Title||Nuclear PTEN tumor-suppressor functions through maintaining heterochromatin structure.|
|Abstract Text||The tumor suppressor, PTEN, is one of the most commonly mutated genes in cancer. Recently, PTEN has been shown to localize in the nucleus and is required to maintain genomic stability. Here, we show that nuclear PTEN, independent of its phosphatase activity, is essential for maintaining heterochromatin structure. Depletion of PTEN leads to loss of heterochromatic foci, decreased chromatin compaction, overexpression of heterochromatic genes, and reduced protein stability of heterochromatin protein 1 α. We found that the C-terminus of PTEN is required to maintain heterochromatin structure. Additionally, cancer-associated PTEN mutants lost their tumor-suppressor function when their heterochromatin structure was compromised. We propose that this novel role of PTEN accounts for its function in guarding genomic stability and suppressing tumor development.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|PTEN||Y336*||nonsense||loss of function||PTEN Y336* results in a premature truncation within the C2 tensin-type domain of the Pten protein at amino acid 336 of 403 (UniProt.org). Y336* inhibits Akt phosphorylation and associates with heterochromatin to similar levels of wild-type Pten, but fails to stabilize Hp1alpha protein and enhances Hp1alpha polyubiquitination, leading to satellite DNA overexpression, failure to suppress cell growth, arrest cycle cycle progression, or inhibit transformation in cultured cells (PMID: 25946202).|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|PTEN Y336*||breast cancer||sensitive||Talazoparib||Preclinical - Cell culture||Actionable||In a preclinical study, breast cancer cells expressing PTEN Y336* demonstrated increased sensitivity to Talzenna (talazoparib) compared to cells expressing wild-type Pten in culture (PMID: 25946202}.||25946202|