Báo cáo khoa học: TORC-SIK cascade regulates CREB activity through the basic leucine zipper domain

TORC-SIK cascade regulates CREB activity through the basic leucine zipper domain

Tác giả: Hiroshi Takemori, Junko Kajimura, Mitsuhiro Okamoto

Lĩnh vực: The transcription factor cAMP response element-binding protein (CREB) plays important roles in gene expression induced by cAMP signaling and is believed to be activated when its Ser133 is phosphorylated. However, the discovery of Ser133-independent activation by the activation of transducer of regulated CREB activity coactivators (TORC) and repression by salt inducible kinase cascades suggests that Ser133-independent regulation of CREB is also important. The activation and repression are mediated by the basic leucine zipper domain of CREB. This review focuses on the basic leucine zipper domain in the regulation of transcriptional activity of CREB and describes the functions of TORC and salt inducible kinase.

Nội dung tài liệu:

• The cAMP response element-binding protein (CREB) is a basic leucine zipper (bZIP) transcription factor that shares properties with other CREB members, the CRE-modulator (CREM) and activating transcription factor 1 (ATF1).
• CREB members are approximately 70% homologous overall, and are more than 90% homologous within their bZIPs and core sequences in the transactivation domain, known as the kinase inducible domain (KID).
• Serine residue 133 (Ser133) in the KID of CREB and the equivalent residues of CREM/ATF1 are phosphorylated by a variety of kinases, whereas the phospho-KID facilitates recruitment of the coactivators CREB-binding protein (CBP) and p300, which enhances CRE-dependent transcription.
• This article summarizes a new insight into bZIP for the regulation of CREB activity, which is played by the coactivator transducer of regulated CREB activity (TORC) and its repressor salt inducible kinase (SIK).

Mục lục chi tiết:

• Introduction
• Importance of bZIP for the action of CREB
• The bZIP domain of CREB interacts with a variety of cellular factors
• The bZIP-binding coactivator TORC
• SIK represses CREB activity via the bZIP domain
• PKA attenuates the CREB repressing activity of SIK1 by phosphorylating at Ser577
• SIK phosphorylates TORC
• LKB regulates CREB activity via the SIK-TORC system
• Inactivation of kinase cascades up-regulates CREB activity via dephosphorylation of TORC
• AMPK against aminoimidazole-4-carboxamide-1-ẞ-4-ribofuranoside (AICAR) enhances TORC phosphorylation
• How A-CREB inhibits CRES
• Future aspects
• References