Disease-Associated Mutations of the STAT5B SH2 Domain Regulate Cytokine-Driven Enhancer Function and Mammary Development

Philips RL, Wang Y, Cheon H, Kanno Y, Gadina M, Sartorelli V, Horvath CM, Darnell JE Jr., Stark GR, O’Shea JJ. The JAK-STAT pathway at 30: much learned, much more to do. Cell. 2022;185(21):3857–76.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Yao Z, Cui Y, Watford WT, Bream JH, Yamaoka K, Hissong BD, Li D, Durum SK, Jiang Q, Bhandoola A, et al. Stat5a/b are essential for normal lymphoid development and differentiation. Proc Natl Acad Sci U S A. 2006;103(4):1000–5.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Miyoshi K, Shillingford JM, Smith GH, Grimm SL, Wagner KU, Oka T, Rosen JM, Robinson GW, Hennighausen L. Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium. J Cell Biol. 2001;155(4):531–42.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Liu X, Robinson GW, Wagner KU, Garrett L, Wynshaw-Boris A, Hennighausen L. Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev. 1997;11(2):179–86.

Article  PubMed  CAS  Google Scholar 

Cui Y, Riedlinger G, Miyoshi K, Tang W, Li C, Deng CX, Robinson GW, Hennighausen L. Inactivation of Stat5 in mouse mammary epithelium during pregnancy reveals distinct functions in cell proliferation, survival, and differentiation. Mol Cell Biol. 2004;24(18):8037–47.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Davey HW, Park SH, Grattan DR, McLachlan MJ, Waxman DJ. STAT5b-deficient mice are growth hormone pulse-resistant. Role of STAT5b in sex-specific liver p450 expression. J Biol Chem. 1999;274(50):35331–6.

Article  PubMed  CAS  Google Scholar 

Klover P, Hennighausen L. Postnatal body growth is dependent on the transcription factors signal transducers and activators of transcription 5a/b in muscle: a role for autocrine/paracrine insulin-like growth factor I. Endocrinology. 2007;148(4):1489–97.

Article  PubMed  CAS  Google Scholar 

Hwa V. Human growth disorders associated with impaired GH action: defects in STAT5B and JAK2. Mol Cell Endocrinol. 2021;519:111063.

Article  PubMed  CAS  Google Scholar 

Holloway MG, Cui Y, Laz EV, Hosui A, Hennighausen L, Waxman DJ. Loss of sexually dimorphic liver gene expression upon hepatocyte-specific deletion of Stat5a-Stat5b locus. Endocrinology. 2007;148(5):1977–86.

Article  PubMed  CAS  Google Scholar 

Wakao H, Gouilleux F, Groner B. Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response. Embo J. 1994;13(9):2182–91.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Liu X, Robinson GW, Gouilleux F, Groner B, Hennighausen L. Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue. Proc Natl Acad Sci U S A. 1995;92(19):8831–5.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Azam M, Erdjument-Bromage H, Kreider BL, Xia M, Quelle F, Basu R, Saris C, Tempst P, Ihle JN, Schindler C. Interleukin-3 signals through multiple isoforms of Stat5. Embo J. 1995;14(7):1402–11.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Mui AL, Wakao H, O’Farrell AM, Harada N, Miyajima A. Interleukin-3, granulocyte-macrophage colony stimulating factor and interleukin-5 transduce signals through two STAT5 homologs. Embo J. 1995;14(6):1166–75.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Yamaji D, Kang K, Robinson GW, Hennighausen L. Sequential activation of genetic programs in mouse mammary epithelium during pregnancy depends on STAT5A/B concentration. Nucleic Acids Res. 2013;41(3):1622–36.

Article  PubMed  CAS  Google Scholar 

Shin HY, Willi M, HyunYoo K, Zeng X, Wang C, Metser G, Hennighausen L. Hierarchy within the mammary STAT5-driven wap super-enhancer. Nat Genet. 2016;48(8):904–11.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Lee HK, Willi M, Kuhns T, Liu C, Hennighausen L. Redundant and non-redundant cytokine-activated enhancers control Csn1s2b expression in the lactating mouse mammary gland. Nat Commun. 2021;12(1):2239.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Lee HK, Willi M, Liu C, Hennighausen L. Cell-specific and shared regulatory elements control a multigene locus active in mammary and salivary glands. Nat Commun. 2023;14(1):4992.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kang K, Yamaji D, Yoo KH, Robinson GW, Hennighausen L. Mammary-specific gene activation is defined by progressive recruitment of STAT5 during pregnancy and the establishment of H3K4me3 marks. Mol Cell Biol. 2014;34(3):464–73.

Article  PubMed  PubMed Central  Google Scholar 

Shillingford JM, Miyoshi K, Robinson GW, Grimm SL, Rosen JM, Neubauer H, Pfeffer K, Hennighausen L. Jak2 is an essential tyrosine kinase involved in pregnancy-mediated development of mammary secretory epithelium. Mol Endocrinol. 2002;16(3):563–70.

Article  PubMed  CAS  Google Scholar 

Bhattacharya D, Teramo A, Gasparini VR, Huuhtanen J, Kim D, Theodoropoulos J, Schiavoni G, Barila G, Vicenzetto C, Calabretto G, et al. Identification of novel STAT5B mutations and characterization of TCRbeta signatures in CD4 + T-cell large granular lymphocyte leukemia. Blood Cancer J. 2022;12(2):31.

Article  PubMed  PubMed Central  Google Scholar 

Rajala HL, Eldfors S, Kuusanmaki H, van Adrichem AJ, Olson T, Lagstrom S, Andersson EI, Jerez A, Clemente MJ, Yan Y, et al. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood. 2013;121(22):4541–50.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kiel MJ, Velusamy T, Rolland D, Sahasrabuddhe AA, Chung F, Bailey NG, Schrader A, Li B, Li JZ, Ozel AB, et al. Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia. Blood. 2014;124(9):1460–72.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Lee HK, Smith HE, Liu C, Willi M, Hennighausen L. Cytosine base editor 4 but not adenine base editor generates off-target mutations in mouse embryos. Commun Biol. 2020;3(1):19.

Article  PubMed  PubMed Central  Google Scholar 

Lee HK, Willi M, Miller SM, Kim S, Liu C, Liu DR, Hennighausen L. Targeting fidelity of adenine and cytosine base editors in mouse embryos. Nat Commun. 2018;9(1):4804.

Article  PubMed  PubMed Central  Google Scholar 

Kaneko T. Genome editing in mouse and rat by electroporation. Methods Mol Biol. 2023;2637:125–34.

Article  PubMed  CAS  Google Scholar 

Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for illumina sequence data. Bioinformatics. 2014;30(15):2114–20.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15–21.

Article  PubMed  CAS  Google Scholar 

Anders S, Pyl PT, Huber W. HTSeq–a python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31(2):166–9.

Article 

Comments (0)

No login
gif