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 SOX9
Homo sapiens
 HIF1A
Homo sapiens
 Pax6
Mus musculus
 PAX6
Homo sapiens
 Snai2
Mus musculus
 PPARA
Homo sapiens
 Ppara
Mus musculus
 Thrb
Mus musculus
 SNAI2
Homo sapiens
 Tbr1
Mus musculus
Transcription Factor Encyclopedia  BETA
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Isoforms
No annotation is available in this section for this article. The content below is taken from a related TF, PAX8 (Homo sapiens).

The human PAX8 gene generates six alternatively spliced transcripts encoding different PAX8 isoforms[1][2]. The PAX8a mRNA contains the coding information of all 10 exons and directs the synthesis of a full-lenght PAX8 protein. The PAX8b transcript arose by skipping the entire exon 8 thus leading to in-frame fusion of exon 7 to exon 9. The PAX8c mRNA lacks exons 7 and 8 leading a shift in reading frame and a premature termination of translation and giving rise to a PAX8 isoform with a proline-rich C terminus. In addition, the use of an internal site of splicing in the middle of exon 8 results in the transcript PAX8d. PAX8e and PAX8f were observed only in the placenta where the isoforms c and d are not present. Expression of these latter mRNAs is high at early embryonic stages and is gradually reduced until PAX8a is the predominant transcript. All PAX8 isoforms contain the conserved paired domain as their DNA-binding motif while differ in their carboxy-terminal regions. It is of interest to note that alternative splicing of PAX8 gene transcripts not only generates six different PAX8 variants but is also temporally and spatially regulated during early mouse development.

References
  1. Kozmik Z et al. Alternative splicing of Pax-8 gene transcripts is developmentally regulated and generates isoforms with different transactivation properties. Mol. Cell. Biol., 13(10):6024-35. (PMID 8413205)
  1. Poleev A et al. Distinct functional properties of three human paired-box-protein, PAX8, isoforms generated by alternative splicing in thyroid, kidney and Wilms' tumors. Eur. J. Biochem., 228(3):899-911. (PMID 7737192)
Covalent modifications
No annotation is available in this section for this article. The content below is taken from a related TF, PAX8 (Homo sapiens).

Despite the critical role played by PAX8 during thyroid development and differentiation, very little is known on its post-translational modifications and on how these modifications may regulate its activity. Thyroid cell growth and differentiation depend on thyrotropin which, by stimulating cAMP synthesis, activates the cAMP-dependent protein kinase A (PKA). It has been demonstrated that the stimulation of cAMP synthesis augments PAX8-specific transcription in thyroid cells, indicating that PKA is involved in PAX8 activation. Nevertheless, there are not clear experimental data of the phosphorylation of PAX8 by PKA [1]. In addition, very recently it has been revealed that upon Ras activation, there is an immediate global down-regulation of thyroid differentiation, which is associated with an inhibition of the cAMP signaling pathway. Moreover, in this model Ras oncoprotein interferes with the transcriptional activity of PAX8 and elicits a negative effect on PAX8 protein levels[2]. On the other side, there are some evidences on the control of PAX8 transcriptional activity by glutathionylation. Specifically, two cysteine residues present in the paired domain of PAX8 have been shown to be responsible for the redox regulation of PAX8 DNA binding activity[3]. Recently, it has been demonstrated that PAX8 is a substrate for SUMO modification and that sumoylation controls PAX8 protein stability[4].

References
  1. Poleev A et al. Determination of functional domains of the human transcription factor PAX8 responsible for its nuclear localization and transactivating potential. Eur. J. Biochem., 247(3):860-9. (PMID 9288908)
  2. Baratta MG et al. Oncogenic ras blocks the cAMP pathway and dedifferentiates thyroid cells via an impairment of pax8 transcriptional activity. Mol. Endocrinol., 23(6):838-48. (PMID 19282367)
  1. Cao X et al. Glutathionylation of two cysteine residues in paired domain regulates DNA binding activity of Pax-8. J. Biol. Chem., 280(27):25901-6. (PMID 15888455)
  2. de Cristofaro T et al. Pax8 protein stability is controlled by sumoylation. J. Mol. Endocrinol., 42(1):35-46. (PMID 18974227)