Recently visited
Please sign in to see a list of articles you recently visited.
Recently updated
 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
Comments (post)
There are no comments posted here... Yet.
Overview
No annotation is available in this section for this article. The content below is taken from a related TF, ZBTB16 (Homo sapiens).

ZBTB16 (zinc finger and BTB-containing protein 16) is more commonly known as, and hereafter described as, promyelocytic leukemia zinc finger or PLZF. PLZF is a transcriptional regulator that belongs to the family of BTB/POZ-zinc finger (Broad complex, Tramtrack, Bric-a-brac (BTB) or poxvirus and zinc finger (POZ)) transcription factors[1]. The BTB/POZ-zinc finger family is characterized by a conserved amino-terminal BTB/POZ protein-protein interaction domain and carboxy-terminal zinc fingers. Similar to other members of this family (there are approximately 60 human BTB/POZ-zinc fingers, including HIC-1, BCL-6, Kaiso, FAZF and LRF), PLZF has transcriptional repressor activity. BTB/POZ-zinc finger transcription factors interact with specific DNA sequences via their zinc finger motifs (generally the Kruppel-like C2H2 type) and control transcriptional activation or repression through mechanisms involving chromatin modification and remodeling. PLZF interacts directly with HDAC1, mSin3a, SMRT and NCoR via conserved residues in its BTB/POZ domain, and PLZF-mediated transcriptional repression is sensitive to HDAC inhibitors [2][3][4].

The PLZF gene was originally identified as a result of the t(11;17) translocation with the retinoic acid receptor-alpha (RARa) locus that yields a PLZF–RARa fusion oncoprotein in rare cases of the hematological malignancy acute promyelocytic leukemia (APL). In APL, the mutant PLZF–RARa fusion protein inappropriately recruits transcriptional corepressors to RARa genes and behaves as a potent dominant negative inhibitor of wild-type RARa. This ultimately affects the expression of RARa targets such as genes involved in DNA repair, apoptosis and cell cycle.

Wild-type PLZF expression is downregulated in some cancers and is suggested to function as a tumor suppressor. PLZF causes growth suppression and cell cycle arrest, suggesting transcriptional repression mediated by PLZF needs to be bypassed for cells to differentiate and proliferate [5]. PLZF has developmental roles as PLZF null mice exhibit defects in patterning of the limb and axial skeleton and defects in spermatogenesis[6][7]. Additionally, PLZF has a role in the differentiation and function of natural killer T cells, probably through interferon-stimulated gene activation. Interferon-induced PLZF phosphorylation and HDAC1 recruitment have a role in transforming PLZF from a repressor to an activator. PLZF in an activator state has been suggested to regulate antiviral innate immunity and affects NK cell activity[8]. When unphosphorylated and acetylated by a histone acetyltranferase, PLZF acts as a repressor and regulates development, cell growth, and apoptosis. The consensus DNA binding site of PLZF has been reported and this motif is present near the promoters of many of its target genes. Additionally, the discovery that PLZF repressor activity can be regulated by posttranslation modifications, in conjunction with its specific developmental roles, suggest that there are many other yet undiscovered roles for this transcriptional regulator. Further binding site analysis and target gene discovery will provide more insight into its cellular function with respect to development and human cancer.

References
  1. Kelly KF and Daniel JM. POZ for effect--POZ-ZF transcription factors in cancer and development. Trends Cell Biol., 16(11):578-87. (PMID 16996269)
  2. Hong SH et al. SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia. Proc. Natl. Acad. Sci. U.S.A., 94(17):9028-33. (PMID 9256429)
  3. Guidez F et al. Histone acetyltransferase activity of p300 is required for transcriptional repression by the promyelocytic leukemia zinc finger protein. Mol. Cell. Biol., 25(13):5552-66. (PMID 15964811)
  4. Melnick A et al. Critical residues within the BTB domain of PLZF and Bcl-6 modulate interaction with corepressors. Mol. Cell. Biol., 22(6):1804-18. (PMID 11865059)
  1. Shaknovich R et al. The promyelocytic leukemia zinc finger protein affects myeloid cell growth, differentiation, and apoptosis. Mol. Cell. Biol., 18(9):5533-45. (PMID 9710637)
  2. Ivins S et al. Regulation of Hoxb2 by APL-associated PLZF protein. Oncogene, 22(24):3685-97. (PMID 12802276)
  3. Costoya JA et al. Essential role of Plzf in maintenance of spermatogonial stem cells. Nat. Genet., 36(6):653-9. (PMID 15156143)
  4. Xu D et al. Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity. Immunity, 30(6):802-16. (PMID 19523849)
Figures
No annotation is available in this section for this article. The content below is taken from a related TF, ZBTB16 (Homo sapiens).
FIGURE 1 PLZF recruits repressive complexes to gene targets
PLZF interacts with specific DNA sequences and recruits transcriptional corepressor complexes to control gene repression. PLZF interacts directly with the transcriptional corepressors Nuclear corepressor (NCoR), histone deacetylase I (HDACI), silencing mediator of retinoid and thyroid hormone receptors (SMRT) and mammalian Swi-independent 3A (mSin3a).
This figure was created by the authors of this article. The authors of this article have provided the assurance that this figure constitutes their original work.