POU-domain proteins Pit-1 and Oct-1 interact to form a heteromeric complex and can cooperate to induce expression of the prolactin promoter.

Voss, Jeffrey W.; Wilson, Lindsay; Rosenfeld, Michael G.

doi:10.1101/gad.5.7.1309

Cited by 197 publications

(128 citation statements)

References 53 publications

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“…A similar mode of DNA interaction is displayed by the Oct-1 POU domain protein (1,20,33,38). Although it has been suggested that GHF-1 homodimerizes in solution and can also form heterodimers with Oct-1 (39,40), most of these interactions have been found to be DNA dependent (21) and the predominant mode of DNA binding most likely involves cooperative binding of two GHF-1 molecules to each binding site composed of two half sites positioned one helical turn apart from each other, in a head-to-tail manner (reviewed in reference 36). These conclusions are consistent with the three-dimensional structure of the Oct-1 DNA binding domain-octamer site complex (19).…”

mentioning

confidence: 92%

M-Phase-Specific Phosphorylation of the POU Transcription Factor GHF-1 by a Cell Cycle-Regulated Protein Kinase Inhibits DNA Binding

Caelles

Hennemann

Karin

1995

Molecular and Cellular Biology

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GHF-1 is a member of the POU family of homeodomain proteins. It is a cell-type-specific transcription factor responsible for determination and expansion of growth hormone (GH)-and prolactin-expressing cells in the anterior pituitary. It was previously suggested that cyclic AMP (cAMP)-responsive protein kinase A (PKA) phosphorylates GHF-1 at a site within the N-terminal arm of its homeodomain, thereby inhibiting its binding to the GH promoter. These results, however, are inconsistent with the physiological stimulation of GH production by the cAMP pathway. As reported here, cAMP agonists and PKA do not inhibit GHF-1 activity in living cells and although they stimulate the phosphorylation of GHF-1, the inhibitory phosphoacceptor site within the homeodomain is not affected. Instead, this site, Thr-220, is subject to M-phase-specific phosphorylation. As a result, GHF-1 DNA binding activity is transiently inhibited during the M phase. This activity is regained once cells enter G 1 , a phase during which GHF-1 phosphorylation is minimal. Thr-220 of GHF-1 is the homolog of the mitotic phosphoacceptor site responsible for the M-phase-specific inhibition of Oct-1 DNA binding Ser-382. As this site is conserved in all POU proteins, it appears that all members of this group are similarly regulated. A specific kinase activity distinct in its substrate specificity and susceptibility to inhibitors from the Cdc2 mitotic kinase or PKA was identified in extracts of mitotic cells. This novel activity could be involved in regulating the DNA binding activity of all POU proteins in a cell cycle-dependent manner.

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mentioning

confidence: 92%

M-Phase-Specific Phosphorylation of the POU Transcription Factor GHF-1 by a Cell Cycle-Regulated Protein Kinase Inhibits DNA Binding

Caelles

Hennemann

Karin

1995

Molecular and Cellular Biology

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“…For example, the POU domains of Oct-1 and Oct-2 have been shown to specifically interact with the TATA binding protein TBP, with HMG2, and with a novel B cell-specific coactivator protein OBF-1 [51,53,55]. Likewise, the specific interactions of Oct-1 with both the pituitary transcription factor Pit-1 and the viral transactivator VP16 involve the POU domain [56,57]. In the case of Oct-1 interaction with VP16, the differences in the amino acid sequence between Oct-1 POU and Oct-2 POU that determine differential interaction have been mapped [50,58].…”

Section: Facilitation Of Pou Homeodomain Binding To the Octamer By Hmmentioning

confidence: 99%

High mobility group I/Y protein functions as a specific cofactor for Oct-2A: mapping of interaction domains

Abdulkadir

Casolaro

Tai

et al. 1998

Journal of Leukocyte Biology

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“…The third key mechanism for understanding POU domain flexibility relates to their ability to bind DNA as both monomers and homo-and heterodimers (Kemler et al 1989;LeBowitz et al 1989;Poellinger and Roeder 1989;Ingraham et al 1990;Voss et al 1991;Holloway et al 1995). Pit-I loses ~1200A^ of solvent accessible surface area attributable to dimerization on DNA.…”

Section: Genes and Developmentmentioning

confidence: 99%

“…Oct-1 functions primarily as a monomer, but can also form cooperative homo-and heterodimers with Oct-2 on a site in the immunoglobulin heavy chain promoter (Kemler et al 1989;Poellinger and Roeder 1989). Pit-1 and Oct-1 can also cooperate to form a heterodimer on the prolactin Prl-lP site (Voss et al 1991). A more dramatic example of POU domain flexibility is provided by the neuronal protein Brn-2.…”

mentioning

confidence: 99%

Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility.

Jacobson¹,

Leon-Del-Rio²,

Rosenfeld³

et al. 1997

Genes Dev.

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Pit-1, a member of the POU domain family of transcription factors, characterized by a bipartite DNA-binding domain, serves critical developmental functions based on binding to diverse DNA elements in its target genes. Here we report a high resolution X-ray analysis of the Pit-1 POU domain bound to a DNA element as a homodimer. This analysis reveals that Pit-1 subdomains bind to perpendicular faces of the DNA, rather than opposite faces of the DNA as in Oct-1. This is accomplished by different spacing and orientation of the POU-specific domain. Contrary to previous predictions, the dimerization interface involves the carboxyl terminus of the DNA recognition helix of the homeodomain, which in an extended conformation interacts with specific residues at the amino terminus of helix al and in the loop between helices a3 and a4 of the POU-specific domain of the symmetry related monomer. These features suggest the molecular basis of disease-causing mutations in Pit-1 and provide potential basis for the flexible allostery between protein domains and DNA sites in the activation of target genes.[Key Words: Crystal structure; Pit-1; POU-domain factors; dimerization; spacing; orientation] Received October 25, 1996; revised version accepted December 3, 1996.The expression of specific genes in cells is often governed by families of transcription factors harboring DNA-binding motifs. In eukaryotes, these factors often exhibit extraordinary versatility. For instance, the bZip and helix-loop-helix families of transcription factors bind to DNA as both homo-and heterodimers (Bexevanis and Vinson 1993;Glover and Harrison 1995). The nuclear receptors go a step further and recognize DNA elements with different spacings and polarities between the half-sites (Naar et al. 1991;Umesono et al. 1991;Kurokawa et al. 1993). The POU domain family of transcription factors are perhaps the most remarkable in their ability to bind DNA as both monomers and dimers and in their ability to adopt diverse configurations (Wegner et al. 1993;Herr and Cleary 1995). Part of this versatility derives from their unusual bipartite structure, consisting of a highly conserved -75 amino acid POUspecific domain (POUg), tethered by a linker of variable length and composition, to a 60-amino-acid homeodomain (POUH). The flexibility of the linker, in particular, allows the possibility of different relative spacings and orientations between the subdomains. This helps to exThese authors contributed equally to this work. "Corresponding author. Present address:

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POU-domain proteins Pit-1 and Oct-1 interact to form a heteromeric complex and can cooperate to induce expression of the prolactin promoter.

Cited by 197 publications

References 53 publications

M-Phase-Specific Phosphorylation of the POU Transcription Factor GHF-1 by a Cell Cycle-Regulated Protein Kinase Inhibits DNA Binding

M-Phase-Specific Phosphorylation of the POU Transcription Factor GHF-1 by a Cell Cycle-Regulated Protein Kinase Inhibits DNA Binding

High mobility group I/Y protein functions as a specific cofactor for Oct-2A: mapping of interaction domains

Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility.

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