F Mechta-Grigoriou | PubMed Health

PubMed2001

The mammalian Jun proteins: redundancy and specificity.

The AP-1 transcription factor is composed of a mixture of homo- and hetero-dimers formed between Jun and Fos proteins. The different Jun and Fos family members vary significantly in their relative abundance and their interactions with additional proteins generating a complex network of transcriptional regulators. Thus, the functional activity of AP-1 in any given cell depends on the relative amount of specific Jun/Fos proteins which are expressed, as well as other potential interacting proteins. This diversity of AP-1 components has complicated our understanding of AP-1 function and resulted in a paucity of information about the precise role of individual AP-1 members in distinct cellular processes. We shall discuss recent studies which suggest that different Jun and Fos family members may have both opposite and overlapping functions in cellular proliferation and cell fate.

Amino Acid Sequence↗

PubMed2000

Nab proteins mediate a negative feedback loop controlling Krox-20 activity in the developing hindbrain.

The developing vertebrate hindbrain is transiently subdivided along the anterior-posterior axis into metameric units, called rhombomeres (r). These segments constitute units of lineage restriction and display specific gene expression patterns. The transcription factor gene Krox-20 is restricted to r3 and r5, and is required for the development of these rhombomeres. We present evidence that Krox-20 transcriptional activity is under the control of a negative feedback mechanism in the hindbrain. This regulatory loop involves two closely related proteins, Nabl and Nab2, previously identified as antagonists of Krox-20 transcriptional activity in cultured cells. Here we show that in the mouse hindbrain, Nab1 and Nab2 recapitulate the Krox-20 expression pattern and that their expression is dependent on Krox-20 function. Furthermore, misexpression of Nab1 or Nab2 in zebrafish embryos leads to alterations in the expression patterns of several hindbrain markers, consistent with an inhibition of Krox-20 activity. Taken together, these data indicate that Krox-20 positively regulates the expression of its own antagonists and raise the possibility that this negative feedback regulatory loop may play a role in the control of hindbrain development.

3T3 Cells↗