CREB3L4

CREB3L4 Full Name

cAMP responsive element binding protein 3-like 4

CREB3L4 Introduction

cAMP Responsive Element Binding Protein 3 Like 4 is a protein-coding gene that encodes a transcription factor involved in regulating gene expression. It is expressed in specific tissues, with notable presence in cells involved in developmental processes and cellular stress responses. As a transcriptional regulator, it binds to specific DNA sequences to modulate the expression of target genes, playing a role in coordinating cellular processes and adapting to environmental changes. Its unique regulatory capabilities make it an important component of cellular signaling and gene expression networks.The protein encoded by the gene features conserved domains typical of transcription factors, including a DNA-binding domain and a transcriptional activation domain. These structural elements enable it to recognize and bind to specific DNA sequences, as well as interact with other transcriptional regulators to form functional complexes. Its structure supports its role in modulating gene expression, allowing it to activate or repress target genes based on cellular signals. The protein's structural traits also facilitate post-translational modifications that fine-tune its transcriptional activity.

Figure 1.The structure of CREB3L4.

Regulation of CREB3L4 Expression and Activity
CREB3L4 expression and activity are regulated at multiple levels, including transcription, translation, post-translational modification, and proteolytic activation. The CREB3L4 promoter contains binding sites for several transcription factors, including androgen receptor, estrogen receptor, and the unfolded protein response sensor ATF6. In the prostate, CREB3L4 expression is induced by androgens, and this induction is required for the full secretory response of prostatic epithelial cells. In the breast, CREB3L4 is induced by estrogen and by prolactin during lactation. The CREB3L4 mRNA is also subject to alternative splicing, generating isoforms with different coding potentials, though the functional significance of these isoforms is not well understood. The stability and activity of the CREB3L4 protein are regulated by post-translational modifications, including phosphorylation and ubiquitination. Prior to activation, CREB3L4 is bound to the endoplasmic reticulum membrane and can be phosphorylated by various kinases, which may affect its transport to the Golgi or its stability.

Genetic Variants and Links to Human Disease
Common genetic variants in the CREB3L4 gene have been associated with several human diseases in genome-wide association studies. Variants near CREB3L4 have been associated with prostate cancer risk, and one specific variant has been associated with aggressive disease and early onset. In breast cancer, variants in CREB3L4 have been associated with hormone receptor-negative tumors and with resistance to endocrine therapy. Outside of cancer, variants in CREB3L4 have been associated with pancreatic enzyme levels and with risk of pancreatitis. Rare loss-of-function mutations in CREB3L4 have been reported in a small number of individuals with pancreatic insufficiency, but the phenotype is variable, and many carriers of predicted loss-of-function variants are healthy, suggesting that other factors can compensate for CREB3L4 deficiency. No Mendelian disorder has been definitively attributed to CREB3L4 mutations, possibly due to functional redundancy with other CREB3 family members. In particular, CREB3L2 and CREB3L3 have partially overlapping functions with CREB3L4 in the secretory tissues, and they may compensate for its loss in most individuals. However, the combined loss of multiple family members may cause more severe phenotypes, as has been observed in double knockout mouse models.

Alternate Names for CREB3L4

CREB3L4; cAMP responsive element binding protein 3-like 4; JAL; hJAL; ATCE1; CREB3; CREB4; AIBZIP; cyclic AMP-responsive element-binding protein 3-like protein 4; CREB-4