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 journalArticlepeer-review

47 Scopus citations


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
Issue number24
StatePublished - Dec 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Activation of TRAP/Mediator subunit TRAP220/Med1 is regulated by mitogen-activated protein kinase-dependent phosphorylation'. Together they form a unique fingerprint.

Cite this