PARP-14, a member of the B aggressive lymphoma family, transduces survival signals in primary B cells.
Poly(ADP-ribos)ylation is one of the longest-known but most enigmatic posttranslational modifications transducing specific signals. The enzyme responsible for the majority of poly(ADP-ribose) polymerization in cells, PARP-1, promotes DNA repair but also mediates a caspase-independent form of apoptosis in response to stressors such as irradiation. However, the biologic function of most other PARPs is not known. Macro-PARPs constitute one branch of the large family of PARP-like proteins also designated as B aggressive lymphoma proteins (BAL1, 2a/2b, 3, or PARP-9, PARP-14, and PARP-15). To elucidate biologic role(s) of a BAL-family macro-PARP, we analyzed mice deficient in PARP-14, a binding partner of the IL-4-induced transcription factor Stat6. We show here that PARP-14 plays a fundamental role mediating protection against apoptosis in IL-4-treated B cells, including that after DNA damage, and mediates IL-4 effects on the levels of gene products that regulate cell survival, proliferation, and lymphomagenesis. Collectively, the results establish that PARP-14 mediates regulation of gene expression and lymphocyte physiology by IL-4 and has a function distinct from PARP-1. Furthermore, the findings suggest mechanisms by which BAL-family proteins might influence pathologic processes involving B lymphocytes.
Cho
Sung Hoon
SH
Department of Microbiology & Immunology, Vanderbilt University, Nashville, TN 37232, USA.
Goenka
Shreevrat
S
Henttinen
Tiina
T
Gudapati
Prathyusha
P
Reinikainen
Arja
A
Eischen
Christine M
CM
Lahesmaa
Riitta
R
Boothby
Mark
M
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000235:genetics; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D005260:Female; D007070:Immunoglobulin A / Q000276:immunology; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017385:Sequence Homology
D007070:Immunoglobulin A; D009363:Neoplasm Proteins; D015847:Interleukin-4; C522628:Parp14 protein, mouse; C529384:Parp9 protein, mouse; D011065:Poly(ADP-ribose) Polymerases