A noncanonical role for the CKI-RB-E2F cell-cycle signaling pathway in plant effector-triggered immunity.

Effector-triggered immunity (ETI), the major host defense mechanism in plants, is often associated with programmed cell death (PCD). Plants lack close homologs of caspases, the key mediators of PCD in animals. So although the NB-LRR receptors involved in ETI are well studied, how they activate PCD and confer disease resistance remains elusive. We show that the Arabidopsis nuclear envelope protein, CPR5, negatively regulates ETI and the associated PCD through a physical interaction with cyclin-dependent kinase inhibitors (CKIs). Upon ETI induction, CKIs are released from CPR5 to cause overactivation of another core cell-cycle regulator, E2F. In cki and e2f mutants, ETI responses induced by both TIR-NB-LRR and CC-NB-LRR classes of immune receptors are compromised. We further show that E2F is deregulated during ETI, probably through CKI-mediated hyperphosphorylation of retinoblastoma-related 1 (RBR1). This study demonstrates that canonical cell-cycle regulators also play important noncanonical roles in plant immunity.

[1]  Karolina M. Pajerowska-Mukhtar,et al.  The HSF-like Transcription Factor TBF1 Is a Major Molecular Switch for Plant Growth-to-Defense Transition , 2012, Current Biology.

[2]  J. Dangl,et al.  The Disease Resistance Signaling Components EDS1 and PAD4 Are Essential Regulators of the Cell Death Pathway Controlled by LSD1 in Arabidopsis , 2001, The Plant Cell Online.

[3]  Huijun Yang,et al.  Perturbation of cell cycle regulation triggers plant immune response via activation of disease resistance genes , 2013, Proceedings of the National Academy of Sciences.

[4]  F. Ausubel,et al.  Roles of Salicylic Acid, Jasmonic Acid, and Ethylene in cpr-Induced Resistance in Arabidopsis , 2000, Plant Cell.

[5]  W. Crosby,et al.  A plant cyclin-dependent kinase inhibitor gene , 1997, Nature.

[6]  D. Oppenheimer,et al.  SIAMESE, a gene controlling the endoreduplication cell cycle in Arabidopsis thaliana trichomes. , 2000, Development.

[7]  Xin Li,et al.  Nuclear Pore Complex Component MOS7/Nup88 Is Required for Innate Immunity and Nuclear Accumulation of Defense Regulators in Arabidopsis[C][W] , 2009, The Plant Cell Online.

[8]  M. Newman,et al.  Direct interaction between the Arabidopsis disease resistance signaling proteins, EDS1 and PAD4 , 2001, The EMBO journal.

[9]  Xiang-Dong Fu,et al.  Timing of plant immune responses by a central circadian regulator , 2011, Nature.

[10]  Dirk Inzé,et al.  The ins and outs of the plant cell cycle , 2007, Nature Reviews Molecular Cell Biology.

[11]  D. Ginsberg,et al.  E2F - at the crossroads of life and death. , 2008, Trends in cell biology.

[12]  J. Parker,et al.  Characterization of eds1, a mutation in Arabidopsis suppressing resistance to Peronospora parasitica specified by several different RPP genes. , 1996, The Plant cell.

[13]  Zheng Qing Fu,et al.  NPR3 and NPR4 are receptors for the immune signal salicylic acid in plants , 2012, Nature.

[14]  D. Inzé,et al.  The Cyclin-Dependent Kinase Inhibitor KRP2 Controls the Onset of the Endoreduplication Cycle during Arabidopsis Leaf Development through Inhibition of Mitotic CDKA;1 Kinase Complexesw⃞ , 2005, The Plant Cell Online.

[15]  D. Chandran,et al.  Atypical E2F transcriptional repressor DEL1 acts at the intersection of plant growth and immunity by controlling the hormone salicylic acid. , 2014, Cell host & microbe.

[16]  D. Ginsberg,et al.  p53 and E2f: partners in life and death , 2009, Nature Reviews Cancer.

[17]  James M. Roberts,et al.  CDK inhibitors: positive and negative regulators of G1-phase progression. , 1999, Genes & development.

[18]  D. Klessig,et al.  Salicylic Acid, a multifaceted hormone to combat disease. , 2009, Annual review of phytopathology.

[19]  David Mackey,et al.  RIN4 Interacts with Pseudomonas syringae Type III Effector Molecules and Is Required for RPM1-Mediated Resistance in Arabidopsis , 2002, Cell.

[20]  B. Horváth,et al.  Arabidopsis E2FA stimulates proliferation and endocycle separately through RBR‐bound and RBR‐free complexes , 2012, The EMBO journal.

[21]  E. Kipreos,et al.  Multiple degradation pathways regulate versatile CIP/KIP CDK inhibitors. , 2012, Trends in cell biology.

[22]  M. Hülskamp,et al.  CPR5 is involved in cell proliferation and cell death control and encodes a novel transmembrane protein , 2001, Current Biology.

[23]  A. Schnittger,et al.  Cell cycle control across the eukaryotic kingdom. , 2013, Trends in cell biology.

[24]  J. Parker,et al.  Arabidopsis EDS1 Connects Pathogen Effector Recognition to Cell Compartment–Specific Immune Responses , 2011, Science.

[25]  Dirk Inzé,et al.  Genome-Wide Identification of Potential Plant E2F Target Genes1[w] , 2005, Plant Physiology.

[26]  Shui Wang,et al.  Arabidopsis BRCA2 and RAD51 proteins are specifically involved in defense gene transcription during plant immune responses , 2010, Proceedings of the National Academy of Sciences.

[27]  Yujing Wang,et al.  Firefly Luciferase Complementation Imaging Assay for Protein-Protein Interactions in Plants1[C][W][OA] , 2007, Plant Physiology.

[28]  Franky R. G. Terras,et al.  Functional Analysis of Cyclin-Dependent Kinase Inhibitors of Arabidopsis , 2001, The Plant Cell Online.

[29]  R. Innes,et al.  Structure-Function Analysis of the Coiled-Coil and Leucine-Rich Repeat Domains of the RPS5 Disease Resistance Protein1[W][OA] , 2012, Plant Physiology.

[30]  J. Dangl,et al.  Expanded functions for a family of plant intracellular immune receptors beyond specific recognition of pathogen effectors , 2011, Proceedings of the National Academy of Sciences.

[31]  P. Epple,et al.  Arabidopsis Type I Metacaspases Control Cell Death , 2010, Science.

[32]  Jonathan D. G. Jones,et al.  The plant immune system , 2006, Nature.

[33]  A. Schnittger,et al.  Misexpression of the Cyclin-Dependent Kinase Inhibitor ICK1/KRP1 in Single-Celled Arabidopsis Trichomes Reduces Endoreduplication and Cell Size and Induces Cell Death Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.008342. , 2003, The Plant Cell Online.

[34]  James M. Roberts,et al.  CDK Inhibitors : Cell Cycle Regulators and Beyond , 2008 .

[35]  D F Klessig,et al.  The cpr5 mutant of Arabidopsis expresses both NPR1-dependent and NPR1-independent resistance. , 1997, The Plant cell.

[36]  J. Ting,et al.  NLRs at the intersection of cell death and immunity , 2008, Nature Reviews Immunology.

[37]  S. H. Kim,et al.  Pathogen Effectors Target Arabidopsis EDS1 and Alter Its Interactions with Immune Regulators , 2011, Science.

[38]  J. Parker,et al.  Constitutive disease resistance requires EDS1 in the Arabidopsis mutants cpr1 and cpr6 and is partially EDS1-dependent in cpr5. , 2001, The Plant journal : for cell and molecular biology.

[39]  D. Inzé,et al.  Genome-Wide Identification of Potential Plant E2F Target Genes1[w] , 2005, Plant Physiology.

[40]  J. Harbour,et al.  The Rb/E2F pathway: expanding roles and emerging paradigms. , 2000, Genes & development.

[41]  Xinnian Dong,et al.  Systemic acquired resistance. , 2003, Annual review of phytopathology.

[42]  F. Ausubel.  Are innate immune signaling pathways in plants and animals conserved? , 2005, Nature Immunology.