| First Author | Nagamori I | Year | 2005 |
| Journal | Genes Cells | Volume | 10 |
| Issue | 6 | Pages | 575-94 |
| PubMed ID | 15938716 | Mgi Jnum | J:104257 |
| Mgi Id | MGI:3611598 | Doi | 10.1111/j.1365-2443.2005.00860.x |
| Citation | Nagamori I, et al. (2005) Tisp40, a spermatid specific bZip transcription factor, functions by binding to the unfolded protein response element via the Rip pathway. Genes Cells 10(6):575-94 |
| abstractText | TISP40, a mouse spermatid-specific gene, encodes a CREB/CREM family transcription factor that is predominantly expressed during spermiogenesis. We report here that TISP40 generates two types of proteins, Tisp40alpha and Tisp40beta, both of which contain a transmembrane domain and localize to the endoplasmic reticulum (ER). In contrast, mutant proteins lacking the transmembrane domain (Tisp40alpha/betaDeltaTM) primarily localize to the nucleus. Endoglycosidase H treatment shows that the C-terminus of Tisp40alpha/beta is glycosylated. Protease experiments demonstrate that Tisp40alpha/beta are Type II transmembrane proteins that are released into the nucleus by a two-step cleavage mechanism called 'regulated intramembrane proteolysis' (Rip). Unlike previously published observations, Tisp40alpha does not bind to the NF-kappaB site; instead, it specifically binds to the unfolded protein response element (UPRE). Luciferase assays reveal that Tisp40betaDeltaTM activates transcription through UPRE. Northern blot analysis shows that Tisp40alpha/betaDeltaTM proteins up-regulate EDEM (ER degradation of enhancing alpha-manosidase-like protein) mRNA. These observations unveil a novel event in mouse spermiogenesis and show that the final stage of transcriptional regulation is controlled by the Rip pathway. |
