Activation of TRAP/Mediator subunit TRAP220/Med1 is regulated by mitogen-activated protein kinase-dependent phosphorylation

Pradeep K. Pandey, T. S. Udayakumar, Xinjie Lin, Dipali Sharma, Paul S. Shapiro, Joseph D. Fondell

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The TRAP/Mediator coactivator complex serves as a molecular bridge between gene-specific activators and RNA polymerase II. TRAP220/Med1 is a key component of TRAP/Mediator that targets the complex to nuclear hormone receptors and other types of activators. We show here that human TRAP220/Med1 is a specific substrate for extracellular signal-regulated kinase (ERK) of the mitogen-activated protein kinase (MAPK) family. We demonstrate that ERK phosphorylates TRAP220/Med1 in vivo at two specific sites: threonine 1032 and threonine 1457. Importantly, we found that ERK phosphorylation significantly increases the stability and half-life of TRAP220/Med1 in vivo and correlates with increased thyroid hormone receptor-dependent transcription. Furthermore, ERK phosphorylates TRAP220/Med1 in a cell cycle-dependent manner, resulting in peak levels of expression during the G2/M phase of the cell cycle. ERK phosphorylation of ectopic TRAP220/ Med1 also triggered shuttling into the nucleolus, thus suggesting that ERK may regulate TRAP220/Med1 subnuclear localization. Finally, we observed that ERK phosphorylation of TRAP220/Med1 stimulates its intrinsic transcriptional coactivation activity. We propose that ERK-mediated phosphorylation is a regulatory mechanism that controls TRAP220/Med1 expression levels and modulates its functional activity.

Original languageEnglish (US)
Pages (from-to)10695-10710
Number of pages16
JournalMolecular and cellular biology
Volume25
Issue number24
DOIs
StatePublished - Dec 1 2005

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Mediator Complex Subunit 1
Mitogen-Activated Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Phosphorylation
Mediator Complex
Threonine
Cell Cycle
Thyroid Hormone Receptors
RNA Polymerase II
G2 Phase
Cytoplasmic and Nuclear Receptors
Cell Division
Half-Life

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Pandey, Pradeep K. ; Udayakumar, T. S. ; Lin, Xinjie ; Sharma, Dipali ; Shapiro, Paul S. ; Fondell, Joseph D. / Activation of TRAP/Mediator subunit TRAP220/Med1 is regulated by mitogen-activated protein kinase-dependent phosphorylation. In: Molecular and cellular biology. 2005 ; Vol. 25, No. 24. pp. 10695-10710.
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Activation of TRAP/Mediator subunit TRAP220/Med1 is regulated by mitogen-activated protein kinase-dependent phosphorylation. / Pandey, Pradeep K.; Udayakumar, T. S.; Lin, Xinjie; Sharma, Dipali; Shapiro, Paul S.; Fondell, Joseph D.

In: Molecular and cellular biology, Vol. 25, No. 24, 01.12.2005, p. 10695-10710.

Research output: Contribution to journalArticle

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AU - Pandey, Pradeep K.

AU - Udayakumar, T. S.

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AU - Sharma, Dipali

AU - Shapiro, Paul S.

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