The Basic Leucine Zipper Domain of c-Jun Functions in Transcriptional Activation through Interaction with the N Terminus of Human TATA-binding Protein-associated Factor-1 (Human TAFII250)

Lively, Tricia N.; Nguyen, Tuan; Galasinski, Shelly K.; Goodrich, James A.

doi:10.1074/jbc.m400892200

Cited by 19 publications

(14 citation statements)

References 50 publications

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“…A number of factors, including activators (i.e., c-Jun and VP16) and TFIIA, can stimulate TFIID/ promoter binding by derepressing the TAF1-mediated inhibition of TBP (19,(48)(49)(50)(51). TFIIA has also been found to aid conversion of canonical TFIID to the rearranged DNA binding form, likely via disruption of TBP/TAF1 TAND interactions (26,27).…”

Section: Discussionmentioning

confidence: 99%

p53 Dynamically Directs TFIID Assembly on Target Gene Promoters

Coleman

Qiao

Singh

et al. 2017

Molecular and Cellular Biology

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p53 is a central regulator that turns on vast gene networks to maintain cellular integrity in the presence of various stimuli. p53 activates transcription initiation in part by aiding recruitment of TFIID to the promoter. However, the precise means by which p53 dynamically interacts with TFIID to facilitate assembly on target gene promoters remains elusive. To address this key issue, we have undertaken an integrated approach involving single-molecule fluorescence microscopy, single-particle cryo-electron microscopy, and biochemistry. Our real-time single-molecule imaging data demonstrate that TFIID alone binds poorly to native p53 target promoters. p53 unlocks TFIID's ability to bind DNA by stabilizing TFIID contacts with both the core promoter and a region within p53's response element. Analysis of single-molecule dissociation kinetics reveals that TFIID interacts with promoters via transient and prolonged DNA binding modes that are each regulated by p53. Importantly, our structural work reveals that TFIID's conversion to a rearranged DNA binding conformation is enhanced in the presence of DNA and p53. Notably, TFIID's interaction with DNA induces p53 to rapidly dissociate, which likely leads to additional rounds of p53-mediated recruitment of other basal factors. Collectively, these findings indicate that p53 dynamically escorts and loads TFIID onto its target promoters. KEYWORDS p53, TFIID, transcription, structure, single-molecule microscopy M ore than 50% of cancer patients harbor p53 mutations, highlighting the essential role of this protein in tumor suppression (1). To properly maintain genomic stability, p53 induces vast gene networks involved in diverse cellular pathways, including the cell cycle arrest, apoptosis, and DNA repair pathways (2). In response to various stress stimuli, p53 acts as a transcriptional activator that specifically binds consensus response elements (REs; two 10-base-pair half-sites [RRRCWWGYYY]) within its target genes to directly stimulate gene expression (2). p53 utilizes its ability to nonspecifically bind and slide along the DNA to expedite the search for target REs (3). Upon recognition of its response genes, p53 facilitates transcription at least in part by targeting the TFIID-mediated transcription machinery to the promoter (4-7). TFIID is composed of TATA-binding protein (TBP) and 14 TBP-associated factors (TAFs). TFIID recognizes and binds multiple core promoter elements (e.g., the TATA box, the initiator, and downstream core promoter elements [DPE]) surrounding the transcription start site (TSS) (8). Once bound, TFIID serves as a central scaffold for six basal factors, including RNA polymerase II, to form a preinitiation complex (PIC) directing transcription initiation. Importantly, without the assistance of activators such as p53, TFIID's core promoter recognition is weak and rate limiting for transcription initiation due to inefficient PIC assembly (9-16). As TFIID is responsible for transcription of at least ϳ90% of proteincoding genes (17), unraveling how p...

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Section: Discussionmentioning

confidence: 99%

p53 Dynamically Directs TFIID Assembly on Target Gene Promoters

Coleman

Qiao

Singh

et al. 2017

Molecular and Cellular Biology

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“…PU.1, C/EBP␤, or c-Jun have all been reported separately to interact with basal Pol II transcription factors, suggesting that these factors may together facilitate PIC assembly. Indeed, PU.1 was shown to interact with CBP (80), C/EBP␤ with the CRSP130/Sur2 protein present in Mediator complexes or p300 (49,67), and c-Jun with TFIIE, TFIIF, or TAF1 (43,47). Together with our observations of a more efficient recruitment of RNA Pol II, we propose that maximal assembly of PIC on the IL-1␤ promoter is achieved by multiple interactions and recruitment of TFIID and RNA Pol II holoenzymes containing Mediator complexes, CBP/p300, and some general transcription factors by the PU.1-C/EBP␤-c-Jun complex.…”

Section: Discussionmentioning

confidence: 99%

c-Jun Homodimers Can Function as a Context-Specific Coactivator

Grondin

Lefrançois

Tremblay

et al. 2007

Molecular and Cellular Biology

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“…The leucine/isoleucine side chains extend from one ␣-helix to a similar ␣-helix on a second polypeptide. ERK2 and c-Jun were found to homodimerize through a leucine zipper (11,21). In addition, the crystal structure of JNK2␣ revealed that an ␣-helix may encompass the ␣-region, indicating that the leucines/isoleucines within the ␣-region may be a component of a leucine zipper (Fig.…”

Section: Co-immunoprecipitation Indicates That the ␣-Region Is Necessmentioning

confidence: 99%

Constitutive Activity of JNK2α2 Is Dependent on a Unique Mechanism of MAPK Activation

Nitta

Chu

Wong

2008

Journal of Biological Chemistry

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c-Jun N-terminal kinases (JNKs) are part of the mitogen-activated protein kinase (MAPK) family and are important regulators of cell growth, proliferation, and apoptosis. Typically, a sequential series of events are necessary for MAPK activation: phosphorylation, dimerization, and then subsequent translocation to the nucleus. Interestingly, a constitutively active JNK isoform, JNK2␣2, possesses the ability to autophosphorylate and has been implicated in several human tumors, including glioblastoma multiforme. Because overexpression of JNK2␣2 enhances several tumorigenic phenotypes, including cell growth and tumor formation in mice, we studied the mechanisms of JNK2␣2 autophosphorylation and autoactivation. We find that JNK2␣2 dimerization in vitro and in vivo occurs independently of its autophosphorylation but is dependent on nine amino acids, known as the ␣-region. Alanine scanning mutagenesis of the ␣-region reveals that five specific mutants (L218A, K220A, G221A, I224A, and F225A) prevent JNK2␣2 dimerization rendering JNK2␣2 inactive and incapable of stimulating tumor formation. Previous studies coupled with additional mutagenesis of neighboring isoleucines and leucines (I208A, I214A, I231A, and I238A) suggest that a leucine zipper may play an important role in JNK2␣2 homodimerization. We also show that a kinase-inactive JNK2␣2 mutant can interact with and inhibit wild type JNK2␣2 autophosphorylation, suggesting that JNK2␣2 undergoes trans-autophosphorylation. Together, our results demonstrate that JNK2␣2 differs from other MAPK proteins in two major ways; its autoactivation/autophosphorylation is dependent on dimerization, and dimerization most likely precedes autophosphorylation. In addition, we show that dimerization is essential for JNK2␣2 activity and that prevention of dimerization may decrease JNK2␣2 induced tumorigenic phenotypes.

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The Basic Leucine Zipper Domain of c-Jun Functions in Transcriptional Activation through Interaction with the N Terminus of Human TATA-binding Protein-associated Factor-1 (Human TAFII250)

Cited by 19 publications

References 50 publications

p53 Dynamically Directs TFIID Assembly on Target Gene Promoters

p53 Dynamically Directs TFIID Assembly on Target Gene Promoters

c-Jun Homodimers Can Function as a Context-Specific Coactivator

Constitutive Activity of JNK2α2 Is Dependent on a Unique Mechanism of MAPK Activation

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