A model of partnership co-opted by the homeodomain protein TGIF and the Itch/AIP4 ubiquitin ligase for effective execution of TNF-alpha cytotoxicity.

The homeodomain protein TGIF functions as a negative regulator of multiple classes of transcription factors. Here we report on the characterization of TGIF as an essential component of the tumor necrosis factor alpha (TNF-alpha) cytotoxic program. This proapoptotic role of TGIF does not appear to rely on transcriptional modulation but instead is executed in conjunction with Itch/AIP4, an E3 ubiquitin ligase operating in TNF-alpha-induced apoptosis through its ability to target the caspase antagonist cFlip(L) for degradation.

A mechanism for mutational inactivation of the homeodomain protein TGIF in holoprosencephaly.

The homeodomain protein TGIF functions as a negative modulator for multiple classes of transcription factors. Loss of function mutations in a single copy of TGIF result in holoprosencephaly, a developmental anomaly leading to severe forebrain and craniofacial malformations. However, the mechanisms by which these mutations disrupt the functions of TGIF remain to be elucidated.

Human mineralocorticoid receptor A and B protein forms produced by alternative translation sites display different transcriptional activities.

Objective: Aldosterone binds the mineralocorticoid receptor (MR) and is involved in the regulation of ionic transport, mainly sodium retention. MR is encoded by one single gene transcribed into various messengers that are thought to be translated into a unique 107 kDa protein. The aim of this study was to identify and characterize translation initiation variants of the human MR protein.