Knocking off SOCS genes in the mammary gland.
Suppressors of cytokine signaling (SOCS) proteins are critical regulators of cytokine-mediated responses in diverse tissues. In the mammary gland, signal transduction pathways elicited by cytokines and hormones have been shown to control distinct stages of development. In vivo evidence points to essential roles for Socs1 and Socs2 as key physiological attenuators of prolactin receptor (PRLR) signaling during pregnancy and lactogenesis. Recently, Socs3 has been shown to be a critical regulator of involution, the coordinated process of programmed cell death and tissue remodelling that is initiated after the cessation of lactation. This review will predominantly focus on the anti-apoptotic function of Socs3 during mammary gland involution in which it acts as a key attenuator of Stat3-mediated signal transduction. Perturbation of this pathway leads to an increase in the levels of c-myc and its likely target genes, p53, bax and E2F-1, providing evidence that c-myc is a central effector of apoptosis during involution.
Sutherland
Kate D
KD
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Lindeman
Geoffrey J
GJ
Visvader
Jane E
JE
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins