| Abstrakt: |
At the onset of Drosophilametamorphosis the steroid hormone ecdysone induces a process leading to a rapid degeneration of the larval salivary glands (SGs). Ecdysone acts through the ecdysone receptor heterodimer, which activates primary response genes. In particular these genes include the Broad-Complex (BR-C)gene encoding a set of BTB/POZ-transcription factors, among which the Z1 isoform is critical for SG cell death. The timing of SG disappearance depends upon of p127l(2)gl, a cytoskeletal tumor suppressor that interacts with nonmuscle myosin II heavy chain (nmMHC) encoded by the zipper (zip)gene. Reduced l(2)glexpression delays SG histolysis whereas over-expression accelerates this process without affecting larval and pupal development. However, the mechanism by which l(2)glcontrols SG histolysis remains yet unknown. Here we analyze the regulation controlled by p127l(2)gland nmMHC in the cytoplasm on the association of BR-C Z1 with chromatin and remodeling factors, such as Rpd3, Sin3A, and Smrter. In wild-type SGs these factors bind to chromatin but in l(2)glSGs they accumulate in the cytoplasm and the cortical nuclear zone (CNZ). Similar chromatin exclusion occurs in SGs of developmentally delayed zipE(br)/+larvae or can be achieved by high levels of nmMHC synthesis. The present data show that p127l(2)gland nmMHC regulate the access of BR-C Z1, Rpd3, Sin3A, and Smrter to chromatin. As the interaction between p127l(2)gland nmMHC occurs in the cytoplasm, we propose that these nuclear factors are processed by p127l(2)gland then released from p127l(2)glby nmMHC to allow their binding to chromatin. This process may constitute a novel mechanism of gene regulation, which in the absence of p127l(2)gl, or excessive amounts of nmMHC, could lead to a fixed configuration in the pattern of gene expression that prevents further progression of SG differentiation, and programmed cell death (PCD). Such a transcriptional block could play a critical role in the neoplastic transformation of l(2)gltissues. |
