The role of transforming growth factor beta signaling in messenger RNA stability.
Transforming growth factor beta (TGF-beta) is a biologically multipotent regulatory protein implicated in functions that include the regulation of cellular growth, differentiation, extracellular matrix formation, and wound healing. It also plays a role in the pathologies of Alzheimer's disease, cancer and autoimmune disorders. TGF-beta modulates gene expression by affecting transcriptional activation and mRNA turnover rate. Steady-state mRNA levels depend on both the transcriptional activity and mRNA half-life. The stability of mRNA can be modified by the binding of trans-acting factors to cis-elements on the message. These can protect the mRNA from cleavage by RNAses, or they may promote mRNA cleavage. Changes in mRNA stability can lead to changes in the proteome and subsequently in cellular metabolism. The SMAD family of proteins has been implicated in the transduction of the TGF-beta signal, where they regulate transcriptional activity. This review attempts to provide new insights into the role played by TGF-beta in the regulation of mRNA turnover.
Dibrov
Alexander
A
University of Manitoba, Winnipeg, Man., Canada.
Kashour
Tarek
T
Amara
Francis M
FM
D020413:3' Untranslated Regions / Q000378:metabolism; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012264:Ribonucleotide Reductases / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*
D020413:3' Untranslated Regions; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger; D051785:Smad Proteins; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta; C098946:hyaluronan-mediated motility receptor; D051546:Cyclooxygenase 2; D012264:Ribonucleotide Reductases; C108427:ribonucleotide reductase R2 subunit