title: A mix of S and ΔS variants of STAT3 enable survival of activated B-cell-like diffuse large B-cell lymphoma cells in culture.
abstract: Activated B-cell-like diffuse large B-cell lymphoma (ABC DLBCL) is characterized by increased expression and activator of signal transducer and activator of transcription 3 (STAT3). ABC DLBCL cells require STAT3 for growth in culture. In ABC DLBCL cells, eosinophils and perhaps all cells, four variant STAT3 mRNAs (Sα, ΔSα, Sβ and ΔSβ) are present as a result of two alternative splicing events, one that results in the inclusion of a 55-residue C-terminal transactivation domain (α) or a truncated C-terminal domain with 7 unique residues (β) and a second that includes (S) or excludes (ΔS) the codon for Ser-701 in the linker between the SH2 and C-terminal domains. A substantial literature indicates that both α and β variants are required for optimal STAT3 function, but nothing is known about functions of ΔS variants. We used a knockdown/re-expression strategy to explore whether survival of ABC DLBCL cells requires that the four variants be in an appropriate ratio. No single variant rescued survival as well as STAT3Sα-C, Sα with activating mutations (A661C and N663C) in the SH2 domain. Better rescue was achieved when all four variants were re-expressed or Sα and ΔSα or Sβ and ΔSβ were re-expressed in pairs. Rescue correlated with expression of STAT3-sensitive genes NFKBIA and NFKBIZ. We consider a variety of explanations why a mix of S and ΔS variants of STAT3 should enable survival of ABC DLBCL cells.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.|Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: M
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Turton
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: F
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Grindle
authors.affiliation: Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Annis
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Drennan
authors.affiliation: Department of Internal Medicine, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Tweardy
authors.affiliation: Department of Internal Medicine, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: U
authors.initials: U
authors.lastname: Bharadwaj
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.|Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Mosher
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: L
authors.initials: L
authors.lastname: Rui