Disease relevance of PHLDA1

• Constitutive PHLDA1 expression greatly enhances the sensitivity of human melanoma cells to the chemotherapeutic agents doxorubicin and camptothecin [1].
• These results suggest that PHLDA1 is constitutively expressed by melanocytic nevi where it may contribute to their benign phenotype [1].

High impact information on PHLDA1

• Here, we found a proapoptotic Tdag51 (T-cell death associated gene 51) gene as a direct target gene of HSF1 [2].
• Analysis of Tdag51-null testes showed that Tdag51 played substantial roles in promoting heat shock-induced cell death in vivo [2].
• Tdag51, but not major Hsps, were induced in male germ cells exposed to high temperatures [2].
• Hsps bound directly to the N-terminal pleckstrin-homology like (PHL) domain of Tdag51, and suppressed death activity of the C-terminal proline/glutamine/histidine-rich domain [2].
• Our results indicate that the expression of TDAG51 in human T-cells does not correlate with AICD [3].

Biological context of PHLDA1

• The progressive loss of PHLDA1 expression in melanomas may play a role in deregulated cell growth and apoptosis resistance in these tumors [1].
• Analysis of stable cDNA transfectants in two different cell lines revealed that constitutive PHLDA1 expression is associated with reduced cell growth, cloning efficiency, and colony formation but not with alterations in cell cycle parameters [1].
• Assignment of the human PHLDA1 gene to chromosome 12q15 by radiation hybrid mapping [4].
• No correlation between the effects of inhibitors on TDAG51 expression and cell death was observed [3].
• Furthermore, the inducible overexpression of TDAG51 in TetOn Jurkat cells did not modulate cellular proliferation, phorbolester/ionomycin-induced growth arrest, or the expression of various cell surface molecules [3].

Anatomical context of PHLDA1

• T-cell death-associated gene 51 (TDAG51) has been described to regulate T-cell receptor/CD3-dependent induction of CD95/Fas and subsequent activation-induced cell death (AICD) in a murine T-cell hybridoma [3].
• The human T-cell death-associated gene 51 (TDAG51) is upregulated upon lymphocyte stimulation and in the context of ER stress [5].

Associations of PHLDA1 with chemical compounds

• Inverse RT-PCR was used for detecting doxycycline-induced mRNA expression after viral transduction with a retroviral vector harboring human TDAG51 [6].

Other interactions of PHLDA1

• These data suggest that cell fate on proteotoxic condition is determined at least by balance between Hsp and Tdag51 levels, which are differently regulated by HSF1 [2].
• The biopsy samples were examined with histological and immunohistochemical methods for antigens associated with apoptosis, such as clusterin, CD95, TDAG51 and bcl-2 [7].

References