Phosphorylation of the C-Terminal Domain of RNA Polymerase II by the Extracellular-Signal-Regulated Protein Kinase ERK2

Markowitz, Rhea-Beth; Hermann, April S.; Taylor, Daniel; He, Li; Anthony-Cahill, Spencer J.; Ahn, Natalie G.; Dynan, William S.

doi:10.1006/bbrc.1995.1291

Cited by 10 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Third, H 2 O 2 treatment causes a situation whereby Ser-5 phosphorylation is highly dependent on the MEK1/2 pathway. Given the several reports (9,23,24) showing that ERK1/2, related MAPKs activated by MEK1/2, act as CTD kinases, we tentatively conclude that ERK1/2 are major Ser-5 kinases after H 2 O 2 treatment.…”

Section: H 2 O 2 -Induced Ubiquitination Of Rpb1-supporting

confidence: 56%

A Novel Hydrogen Peroxide-induced Phosphorylation and Ubiquitination Pathway Leading to RNA Polymerase II Proteolysis

Inukai

Yamaguchi

Kuraoka

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

DNA damage-induced ubiquitination of the largest subunit of RNA polymerase II, Rpb1, has been implicated in transcription-coupled repair for years. The studies so far, however, have been limited to the use of bulky helix-distorting DNA damages caused by UV light and cisplatin, which are corrected by the nucleotide excision repair pathway. Non-bulky, non-helix-distorting damages are caused at high frequency by reactive oxygen species in cells and corrected by the base excision repair pathway. Contrary to a classic view, we recently found that the second type of DNA lesions also causes RNA polymerase II stalling in vitro. In this paper, we show that hydrogen peroxide (H 2 O 2 ) causes significant ubiquitination and proteasomal degradation of Rpb1 by mechanisms that are distinct from those employed after UV irradiation. UV irradiation and H 2 O 2 treatment cause characteristic changes in protein kinases phosphorylating the carboxyl-terminal domain at Ser-2 and -5. The H 2 O 2 -induced ubiquitination is likely dependent on unusual Ser-5 phosphorylation by ERK1/2. Moreover, the H 2 O 2 -induced ubiquitination occurs on transcriptionally engaged polymerases without the help of Cockayne syndrome A and B proteins and von Hippel-Lindau tumor suppressor proteins, which are all required for the UV-induced ubiquitination. These results suggest that stalled polymerases are recognized and ubiquitinated differentially depending on the types of DNA lesions. Our findings may have general implications in the basic mechanism of transcriptioncoupled nucleotide excision repair and base excision repair.

show abstract

Section: H 2 O 2 -Induced Ubiquitination Of Rpb1-supporting

confidence: 56%

A Novel Hydrogen Peroxide-induced Phosphorylation and Ubiquitination Pathway Leading to RNA Polymerase II Proteolysis

Inukai

Yamaguchi

Kuraoka

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The substrates tested were MBP (see Fig. 6), c-Jun, JunD, c-Fos, histone H1, histone H3, and the C-terminal domain of RNA polymerase II (CTD), which is phosphorylated by MAP kinases in vitro and whose phosphorylation modulates RNA polymerase II transcriptional activity (51)(52)(53). No detectable kinase activity for any substrate tested was associated with the AP-1 DNA-binding site, although specific association of AP-1 subunits and ERPs with AP-1 DNA was detected in the same experiments by Western blots, and positive control kinase activity with recombinant enzymes was observed (ERK1 enzyme for MBP, CTD, and c-Fos substrates; PKC enzyme for histone H1 and H3 substrates; JNK1 enzyme for MBP, c-Jun and JunD substrates; Fig.…”

Section: Immunoprecipitates Containing Ap-1 and Erps Contain Kinase Amentioning

confidence: 99%

Ten ERK-related Proteins in Three Distinct Classes Associate with AP-1 Proteins and/or AP-1 DNA

Kumar¹,

Bernstein²

2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

We have identified seven ERK-related proteins ("ERPs"), including ERK2, that are stably associated in vivo with AP-1 dimers composed of diverse Jun and Fos family proteins. These complexes have kinase activity. We designate them as "class I ERPs." We originally hypothesized that these ERPs associate with DNA along with AP-1 proteins. We devised a DNA affinity chromatography-based analytical assay for DNA binding, the "nucleotide affinity preincubation specificity test recognition" (NAPSTER) assay. In this assay, class I ERPs do not associate with AP-1 DNA. However, several new "class II" ERPs do associate with DNA. p41 and p44 are ERK1/2-related ERPs that lack kinase activity and associate along with AP-1 proteins with AP-1 DNA. Class I ERPs and their associated kinase activity thus appear to bind AP-1 dimers when they are not bound to DNA and then disengage and are replaced by class II ERPs to form higher order complexes when AP-1 dimers bind DNA. p97 is a class III ERP, related to ERK3, that associates with AP-1 DNA without AP-1 proteins. With the exception of ERK2, none of the 10 ERPs appear to be known mitogen-activated protein kinase superfamily members.

show abstract

“…Serum stimulation of quiescent cells, which can cause Go cells to re-enter the cell cycle, leads to ERK 1/2 induced phosphorylation of the CTD (84,85). In vitro studies indicate a predilection for Serine 5 of the YSPTSPS consensus sequence with no particular preference for consensus vs. nonconsensus heptapeptides (20,86). Heat shock, a model form of stress shown to also inhibit cell cycle progression, activates ERK1/2 and induces extensive CTD phosphorylation (87).…”

Section: Erk 1/2 (Map Kinase)mentioning

confidence: 99%

Cell cycle regulation and RNA polymerase II

Bregman

Pestell²,

Kidd³

2000

Front Biosci

View full text Add to dashboard Cite

The cell cycle and transcription by RNA polymerase II (RNAP II) are closely related. They utilize shared components. RNAP II transcriptional activity is modulated during the cell cycle. Cell cycle dependent changes in the phosphorylation status of the carboxylterminal domain (CTD) of the largest subunit of RNAP II (RNAP II-LS) alter transcription. Several CTD kinases are members of the cyclin-dependent kinase (cdk) superfamily, including p34 cdc2 (cdk1), cdk7, cdk8, and cdk9. Each of these cdks, with their respective cyclin partners, have been linked to cell cycle regulatory events. Other CTD kinases such as casein kinase II (CKII) and c-abl have also been implicated in cell cycle dependent modifications of the CTD. In addition, the stalling of RNAP II complexes at DNA lesions helps stimulate p53 accumulation which largely determines the cell's DNA damage response, including cell cycle arrest. Alzheimer's disease pathology results partially from activation of mitotic cdks in postmitotic neurons which can phosphorylate RNAP II-LS and other targets.

show abstract

Phosphorylation of the C-Terminal Domain of RNA Polymerase II by the Extracellular-Signal-Regulated Protein Kinase ERK2

Cited by 10 publications

References 0 publications

A Novel Hydrogen Peroxide-induced Phosphorylation and Ubiquitination Pathway Leading to RNA Polymerase II Proteolysis

A Novel Hydrogen Peroxide-induced Phosphorylation and Ubiquitination Pathway Leading to RNA Polymerase II Proteolysis

Ten ERK-related Proteins in Three Distinct Classes Associate with AP-1 Proteins and/or AP-1 DNA

Cell cycle regulation and RNA polymerase II

Contact Info

Product

Resources

About