P-TEFb-mediated phosphorylation of hSpt5 C-terminal repeats is critical for processive transcription elongation.
Mol Cell
; 21(2): 227-37, 2006 Jan 20.
Article
en En
| MEDLINE
| ID: mdl-16427012
ABSTRACT
Human DSIF, a heterodimer composed of hSpt4 and hSpt5, plays opposing roles in transcription elongation by RNA polymerase II (RNA Pol II). Here, we describe an evolutionarily conserved repetitive heptapeptide motif (consensus = G-S-R/Q-T-P) in the C-terminal region (CTR) of hSpt5, which, like the C-terminal domain (CTD) of RNA Pol II, is highly phosphorylated by P-TEFb. Thr-4 residues of the CTR repeats are functionally important phosphorylation sites. In vitro, Thr-4 phosphorylation is critical for the elongation activation activity of DSIF, but not to its elongation repression activity. In vivo, Thr-4 phosphorylation is critical for epidermal growth factor (EGF)-inducible transcription of c-fos and for efficient progression of RNA Pol II along the gene. We consider this phosphorylation to be a switch that converts DSIF from a repressor to an activator. We propose the "mini-CTD" hypothesis, in which phosphorylated CTR is thought to function in a manner analogous to phosphorylated CTD, serving as an additional code for active elongation complexes.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Factores de Elongación Transcripcional
/
Factor B de Elongación Transcripcional Positiva
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2006
Tipo del documento:
Article
País de afiliación:
Japón