Gene Symbol: HSL1
Description: protein kinase HSL1
Alias: ELM2, NIK1, protein kinase HSL1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Burton J, Solomon M. Hsl1p, a Swe1p inhibitor, is degraded via the anaphase-promoting complex. Mol Cell Biol. 2000;20:4614-25 pubmed
  2. Sakchaisri K, Asano S, Yu L, Shulewitz M, Park C, Park J, et al. Coupling morphogenesis to mitotic entry. Proc Natl Acad Sci U S A. 2004;101:4124-9 pubmed
    ..Swe1 is recruited to the neck and hyperphosphorylated before ubiquitin-mediated degradation. Hsl1 kinase (Nim1 ortholog), a negative regulator of Wee1, is required for efficient Swe1 localization at the neck but ..
  3. Burton J, Tsakraklides V, Solomon M. Assembly of an APC-Cdh1-substrate complex is stimulated by engagement of a destruction box. Mol Cell. 2005;18:533-42 pubmed
    ..Moreover, an intact D box domain within a substrate was required to stimulate the association between the Cdh1p-substrate complex and the APC. ..
  4. Bouquin N, Barral Y, Courbeyrette R, Blondel M, Snyder M, Mann C. Regulation of cytokinesis by the Elm1 protein kinase in Saccharomyces cerevisiae. J Cell Sci. 2000;113 ( Pt 8):1435-45 pubmed
    ..Genetic and biochemical evidence suggest that Elm1 and the three other septin-localised protein kinases, Hsl1, Gin4 and Kcc4, work in parallel pathways to regulate septin behaviour and cytokinesis...
  5. Shulewitz M, Inouye C, Thorner J. Hsl7 localizes to a septin ring and serves as an adapter in a regulatory pathway that relieves tyrosine phosphorylation of Cdc28 protein kinase in Saccharomyces cerevisiae. Mol Cell Biol. 1999;19:7123-37 pubmed
    ..The HSL1 and HSL7 gene products act as negative regulators of Swe1...
  6. Simpson Lavy K, Sajman J, Zenvirth D, Brandeis M. APC/CCdh1 specific degradation of Hsl1 and Clb2 is required for proper stress responses of S. cerevisiae. Cell Cycle. 2009;8:3003-9 pubmed
    ..Cells expressing stabilized Hsl1 were sensitive to caffeine and failed to activate the Slt2 pathway...
  7. Park C, Song S, Lee P, Shou W, Deshaies R, Lee K. Loss of CDC5 function in Saccharomyces cerevisiae leads to defects in Swe1p regulation and Bfa1p/Bub2p-independent cytokinesis. Genetics. 2003;163:21-33 pubmed
    ..semipermissive temperature, the cdc5-3 mutant exhibited a synergistic bud elongation and growth defect with loss of HSL1, a component important for normal G(2)/M transition...
  8. Passmore L, McCormack E, Au S, Paul A, Willison K, Harper J, et al. Doc1 mediates the activity of the anaphase-promoting complex by contributing to substrate recognition. EMBO J. 2003;22:786-96 pubmed
    ..These results imply that Doc1p/Apc10 may play a role to regulate the binding of specific substrates, similar to that of the coactivators. ..
  9. Lew D. Cell-cycle checkpoints that ensure coordination between nuclear and cytoplasmic events in Saccharomyces cerevisiae. Curr Opin Genet Dev. 2000;10:47-53 pubmed
    ..Thus, specific cell-cycle regulators are well-placed to monitor whether a cell has formed a bud and whether a daughter nucleus has been delivered accurately to the bud following mitosis. ..

More Information


  1. Cid V, Shulewitz M, McDonald K, Thorner J. Dynamic localization of the Swe1 regulator Hsl7 during the Saccharomyces cerevisiae cell cycle. Mol Biol Cell. 2001;12:1645-69 pubmed
    ..Swe1 is itself negatively regulated by Hsl1, a Nim1-related protein kinase, and by Hsl7, a presumptive protein-arginine methyltransferase...
  2. Clotet J, Escote X, Adrover M, Yaakov G, GarĂ­ E, Aldea M, et al. Phosphorylation of Hsl1 by Hog1 leads to a G2 arrest essential for cell survival at high osmolarity. EMBO J. 2006;25:2338-46 pubmed
    ..Activated Hog1 interacts and directly phosphorylates a residue within the Hsl7-docking site of the Hsl1 checkpoint kinase, which results in delocalization of Hsl7 from the septin ring and leads to Swe1 accumulation...
  3. Asano S, Park J, Yu L, Zhou M, Sakchaisri K, Park C, et al. Direct phosphorylation and activation of a Nim1-related kinase Gin4 by Elm1 in budding yeast. J Biol Chem. 2006;281:27090-8 pubmed
    ..Thus, Elm1 regulates the septin assembly-dependent cellular events by directly phosphorylating and activating the Gin4-dependent pathway(s). ..
  4. Szkotnicki L, Crutchley J, Zyla T, Bardes E, Lew D. The checkpoint kinase Hsl1p is activated by Elm1p-dependent phosphorylation. Mol Biol Cell. 2008;19:4675-86 pubmed publisher
    ..We identified elm1 mutants in a screen for defects in Swe1p degradation and show that a phosphomimic T273E mutation in HSL1 bypasses the need for Elm1p in this pathway.
  5. Burton J, Solomon M. Mad3p, a pseudosubstrate inhibitor of APCCdc20 in the spindle assembly checkpoint. Genes Dev. 2007;21:655-67 pubmed
    ..We present a model aimed at unifying previous analyses of checkpoint function by focusing on the Mad3-Cdc20 interaction. ..
  6. Burton J, Xiong Y, Solomon M. Mechanisms of pseudosubstrate inhibition of the anaphase promoting complex by Acm1. EMBO J. 2011;30:1818-29 pubmed publisher
    ..mutations within Acm1 promoted its ubiquitination by APC(Cdh1) whereas lysine removal from the APC substrate Hsl1 converted it into a potent APC(Cdh1) inhibitor...
  7. McMillan J, Longtine M, Sia R, Theesfeld C, Bardes E, Pringle J, et al. The morphogenesis checkpoint in Saccharomyces cerevisiae: cell cycle control of Swe1p degradation by Hsl1p and Hsl7p. Mol Cell Biol. 1999;19:6929-39 pubmed
    ..These findings suggest that Hsl1p and Hsl7p interact directly with Swe1p to promote its recognition by the ubiquitination complex, leading ultimately to its destruction. ..
  8. Barral Y, Parra M, Bidlingmaier S, Snyder M. Nim1-related kinases coordinate cell cycle progression with the organization of the peripheral cytoskeleton in yeast. Genes Dev. 1999;13:176-87 pubmed
    ..The nim1-related protein kinase, Hsl1, induces entry into mitosis by negatively regulating Swe1...
  9. Longtine M, Theesfeld C, McMillan J, Weaver E, Pringle J, Lew D. Septin-dependent assembly of a cell cycle-regulatory module in Saccharomyces cerevisiae. Mol Cell Biol. 2000;20:4049-61 pubmed
    ..cerevisiae, Hsl1p and Kcc4p, produce no detectable effect on septin organization. However, deletion of HSL1, but not of KCC4, did produce a cell cycle delay under some conditions; this delay appears to reflect a direct role ..
  10. Versele M, Thorner J. Septin collar formation in budding yeast requires GTP binding and direct phosphorylation by the PAK, Cla4. J Cell Biol. 2004;164:701-15 pubmed
    ..Cla4 interacts directly with and phosphorylates certain septins in vitro and in vivo. Thus, septin collar formation may correspond to septin filament assembly, and requires both GTP binding and Cla4-mediated phosphorylation of septins. ..
  11. Raspelli E, Cassani C, Lucchini G, Fraschini R. Budding yeast Dma1 and Dma2 participate in regulation of Swe1 levels and localization. Mol Biol Cell. 2011;22:2185-97 pubmed publisher
    ..Taken together, the data highlight a previously unknown role of these proteins in the complex regulation of Swe1 and suggest that they might contribute to control, directly or indirectly, Swe1 ubiquitylation. ..
  12. Simpson Lavy K, Brandeis M. Clb2 and the APC/C(Cdh1) regulate Swe1 stability. Cell Cycle. 2010;9:3046-53 pubmed publisher
    ..The APC/C(Cdh1) substrates Cdc5, Clb2 and Hsl1 regulate Swe1 degradation. We observed that clb2Deltacdh1Delta double mutant S...
  13. Burton J, Solomon M. D box and KEN box motifs in budding yeast Hsl1p are required for APC-mediated degradation and direct binding to Cdc20p and Cdh1p. Genes Dev. 2001;15:2381-95 pubmed
    ..These results indicate that D box and KEN box motifs are important for direct binding to the APC machinery, leading to ubiquitination and subsequent protein degradation. ..
  14. Ostapenko D, Solomon M. Anaphase promoting complex-dependent degradation of transcriptional repressors Nrm1 and Yhp1 in Saccharomyces cerevisiae. Mol Biol Cell. 2011;22:2175-84 pubmed publisher
    ..Therefore, in addition to its known functions, APC-mediated targeting of Nrm1 and Yhp1 coordinates transcription of multiple genes in G1 with other cell cycle events. ..
  15. Ostapenko D, Burton J, Wang R, Solomon M. Pseudosubstrate inhibition of the anaphase-promoting complex by Acm1: regulation by proteolysis and Cdc28 phosphorylation. Mol Cell Biol. 2008;28:4653-64 pubmed publisher
    ..Thus, Cdc28 serves dual roles in inhibiting Cdh1-dependent APC activity during the cell cycle: stabilization of the Cdh1 inhibitor Acm1 and direct phosphorylation of Cdh1 to prevent its association with the APC. ..
  16. Liu H, Wang Y. The function and regulation of budding yeast Swe1 in response to interrupted DNA synthesis. Mol Biol Cell. 2006;17:2746-56 pubmed
    ..Therefore, S-phase accumulated Swe1 prevents Clb2-Cdk1-mediated mitotic activities, but has little effects on Clb5-Cdk1-associated S-phase progression. ..
  17. Hanrahan J, Snyder M. Cytoskeletal activation of a checkpoint kinase. Mol Cell. 2003;12:663-73 pubmed
    ..cytoskeleton is monitored and coordinated with cell cycle progression by analyzing a key regulatory protein kinase, Hsl1, that becomes activated only when the septin cytoskeleton is properly assembled...
  18. Wang R, Burton J, Solomon M. Transcriptional and post-transcriptional regulation of Cdc20 during the spindle assembly checkpoint in S. cerevisiae. Cell Signal. 2017;33:41-48 pubmed publisher
    ..These findings contribute to our understanding of how the inhibition of APCCdc20 activity and enhanced Cdc20 degradation are required for proper spindle checkpoint arrest. ..
  19. Catala M, Aksouh L, Abou Elela S. RNA-dependent regulation of the cell wall stress response. Nucleic Acids Res. 2012;40:7507-17 pubmed publisher
    ..The data supports a model for gene regulation in which nuclear mRNA degradation optimizes the cell response to stress and links it to the cell cycle. ..
  20. Sundin B, Chiu C, Riffle M, Davis T, Muller E. Localization of proteins that are coordinately expressed with Cln2 during the cell cycle. Yeast. 2004;21:793-800 pubmed
    ..A complete list of localizations, along with images, can be found at our website (http://www.yeastrc.org/cln2/). ..
  21. Mizunuma M, Hirata D, Miyahara K, Tsuchiya E, Miyakawa T. Role of calcineurin and Mpk1 in regulating the onset of mitosis in budding yeast. Nature. 1998;392:303-6 pubmed
    ..These cellular pathways also induce a G2-phase delay in response to hypotonic shock. ..
  22. Ma X, Lu Q, Grunstein M. A search for proteins that interact genetically with histone H3 and H4 amino termini uncovers novel regulators of the Swe1 kinase in Saccharomyces cerevisiae. Genes Dev. 1996;10:1327-40 pubmed
    ..One histone synthetic-lethal gene, HSL1, encodes a putative protein kinase that has high sequence and functional homology to fission yeast cdr1/nim1, an ..
  23. Ostapenko D, Burton J, Solomon M. Identification of anaphase promoting complex substrates in S. cerevisiae. PLoS ONE. 2012;7:e45895 pubmed publisher
    ..Thus, the APC/C(Cdh1)-mediated degradation of these proteins may help to coordinate re-entry into the cell cycle following environmental stresses. ..
  24. Geymonat M, Spanos A, Jensen S, Sedgwick S. Phosphorylation of Lte1 by Cdk prevents polarized growth during mitotic arrest in S. cerevisiae. J Cell Biol. 2010;191:1097-112 pubmed publisher
    ..Thus, Lte1 has dual functions for regulation of mitotic progression: it both induces mitotic exit and prevents polarized growth during mitotic arrest, thereby coupling cell cycle progression and morphological development. ..
  25. Girard J, Tenthorey J, Morgan D. An E2 accessory domain increases affinity for the anaphase-promoting complex and ensures E2 competition. J Biol Chem. 2015;290:24614-25 pubmed publisher
    ..The UBA domain is required for normal Ubc1 function and E2 competition in vivo. Thus, the UBA domain of Ubc1 ensures efficient polyubiquitination of substrate by balancing Ubc1 affinity with that of Ubc4. ..
  26. Crutchley J, King K, Keaton M, Szkotnicki L, Orlando D, Zyla T, et al. Molecular dissection of the checkpoint kinase Hsl1p. Mol Biol Cell. 2009;20:1926-36 pubmed publisher
    ..We suggest that Hsl1p responds to alterations in septin organization, which themselves occur in response to the local geometry of the cell cortex. ..
  27. Okuzaki D, Watanabe T, Tanaka S, Nojima H. The Saccharomyces cerevisiae bud-neck proteins Kcc4 and Gin4 have distinct but partially-overlapping cellular functions. Genes Genet Syst. 2003;78:113-26 pubmed
    ..b>Hsl1/Nik1, Kcc4 and Gin4 are structurally homologous protein kinases that localize to the bud neck and negatively ..
  28. Loewen C, Young B, Tavassoli S, Levine T. Inheritance of cortical ER in yeast is required for normal septin organization. J Cell Biol. 2007;179:467-83 pubmed
    ..This perturbation leads to a delay in the transition through G2, activating the Saccharomyces wee1 kinase (Swe1) and the morphogenesis checkpoint. Thus, we identify a mechanism involved in sensing the distribution of ER. ..
  29. Choi E, Dial J, Jeong D, Hall M. Unique D box and KEN box sequences limit ubiquitination of Acm1 and promote pseudosubstrate inhibition of the anaphase-promoting complex. J Biol Chem. 2008;283:23701-10 pubmed publisher
  30. Larson J, Kozubowski L, Tatchell K. Changes in Bni4 localization induced by cell stress in Saccharomyces cerevisiae. J Cell Sci. 2010;123:1050-9 pubmed publisher
  31. Liang F, Jin F, Liu H, Wang Y. The molecular function of the yeast polo-like kinase Cdc5 in Cdc14 release during early anaphase. Mol Biol Cell. 2009;20:3671-9 pubmed publisher
    ..Therefore, we conclude that the down-regulation of Swe1 protein levels by Cdc5 promotes FEAR activation by relieving the inhibition on Clb2-Cdk1, the kinase for Net1 protein. ..
  32. Merlini L, Fraschini R, Boettcher B, Barral Y, Lucchini G, Piatti S. Budding yeast dma proteins control septin dynamics and the spindle position checkpoint by promoting the recruitment of the Elm1 kinase to the bud neck. PLoS Genet. 2012;8:e1002670 pubmed publisher
    ..Altogether, our data indicate that septin dynamics and SPOC function are intimately linked and support the idea that integrity of the bud neck is crucial for SPOC signalling. ..
  33. Wang M, Collins R. A lysine deacetylase Hos3 is targeted to the bud neck and involved in the spindle position checkpoint. Mol Biol Cell. 2014;25:2720-34 pubmed publisher
    ..Our data suggest that Hos3 facilitates cross-talk between the morphogenesis checkpoint and the SPOC as a component of the intricate monitoring of spindle orientation after mitotic entry and before commitment to mitotic exit. ..
  34. Furukawa K, Randhawa A, Kaur H, Mondal A, Hohmann S. Fungal fludioxonil sensitivity is diminished by a constitutively active form of the group III histidine kinase. FEBS Lett. 2012;586:2417-22 pubmed publisher
    ..Our results explain the different reasons for fludioxonil resistance conferred by its deletion and missense mutation. ..
  35. Iwase M, Toh e A. Ybr267w is a new cytoplasmic protein belonging to the mitotic signaling network of Saccharomyces cerevisiae. Cell Struct Funct. 2004;29:1-15 pubmed
    ..In view of the fact that members belonging to the mitotic signaling network are localized to the bud neck, at least at some stage of the cell cycle, Rei1 is a unique component of this pathway. ..
  36. Yano K, Uesono Y, Yoshida S, Kikuchi A, Kashiwazaki J, Mabuchi I, et al. Mih1/Cdc25 is negatively regulated by Pkc1 in Saccharomyces cerevisiae. Genes Cells. 2013;18:425-41 pubmed publisher
    ..These results suggest that Mih1 is negatively regulated by Pkc1-mediated phosphorylation, which excludes it from the nucleus under certain conditions. ..
  37. Zhang Z, Yang J, Kong E, Chao W, Morris E, da Fonseca P, et al. Recombinant expression, reconstitution and structure of human anaphase-promoting complex (APC/C). Biochem J. 2013;449:365-71 pubmed publisher
    ..human APC/C is correctly assembled, as judged by its capacity to ubiquitinate the budding yeast APC/C substrate Hsl1 (histone synthetic lethal 1) dependent on the APC/C co-activator Cdh1 [Cdc (cell division cycle) 20 homologue 1], ..
  38. Ruault M, Pillus L. Chromatin-modifiying enzymes are essential when the Saccharomyces cerevisiae morphogenesis checkpoint is constitutively activated. Genetics. 2006;174:1135-49 pubmed
    ..A catalytically dead Hsl7p retained wild-type interactions, implying that modification of histone H3 or H4 N termini by Gcn5p, Esa1p, Rpd3p, and Set1p, but not by Hsl7p, was needed to bypass the morphogenesis checkpoint. ..
  39. La Valle R, Wittenberg C. A role for the Swe1 checkpoint kinase during filamentous growth of Saccharomyces cerevisiae. Genetics. 2001;158:549-62 pubmed
    In this study we show that inactivation of Hsl1 or Hsl7, negative regulators of the Swe1 kinase, enhances the invasive behavior of haploid and diploid cells...
  40. Okuzaki D, Tanaka S, Kanazawa H, Nojima H. Gin4 of S. cerevisiae is a bud neck protein that interacts with the Cdc28 complex. Genes Cells. 1997;2:753-70 pubmed
    ..The cell cycle regulator Nik1 (Hsl1) is a protein kinase that interacts with the Cdc28 complex...
  41. Tanaka S, Nojima H. Nik1: a Nim1-like protein kinase of S. cerevisiae interacts with the Cdc28 complex and regulates cell cycle progression. Genes Cells. 1996;1:905-21 pubmed
    ..One of the isolated genes was found to encode a putative protein kinase similar to Nim1 of S. pombe and was termed NIK1 (Nim1-like kinase 1). Transcription of NIK1 was periodic and peaked at the G1/S boundary...
  42. Kang H, Tsygankov D, Lew D. Sensing a bud in the yeast morphogenesis checkpoint: a role for Elm1. Mol Biol Cell. 2016;27:1764-75 pubmed publisher
    ..Here we show that recruitment of Hsl7 to the septin ring depends on a combination of two septin-binding kinases: Hsl1 and Elm1...
  43. Mizunuma M, Hirata D, Miyaoka R, Miyakawa T. GSK-3 kinase Mck1 and calcineurin coordinately mediate Hsl1 down-regulation by Ca2+ in budding yeast. EMBO J. 2001;20:1074-85 pubmed
    ..Genetic analyses indicated that Mck1 functions downstream of the Mpk1 pathway and down-regulates Hsl1, an inhibitory kinase of Swe1...
  44. Edgington N, Blacketer M, Bierwagen T, Myers A. Control of Saccharomyces cerevisiae filamentous growth by cyclin-dependent kinase Cdc28. Mol Cell Biol. 1999;19:1369-80 pubmed
    ..In addition, various mutations affecting Hsl1 or Swe1, known or presumed components of a protein kinase cascade that mediates Cdc28 phosphorylation on Y19, ..
  45. Finnigan G, Sterling S, Duvalyan A, Liao E, Sargsyan A, Garcia G, et al. Coordinate action of distinct sequence elements localizes checkpoint kinase Hsl1 to the septin collar at the bud neck in Saccharomyces cerevisiae. Mol Biol Cell. 2016;27:2213-33 pubmed publisher
    ..An essential component of this checkpoint is the large (1518-residue) protein kinase Hsl1, which localizes to the bud neck only if the septin collar has been correctly formed...
  46. King K, Jin M, Lew D. Roles of Hsl1p and Hsl7p in Swe1p degradation: beyond septin tethering. Eukaryot Cell. 2012;11:1496-502 pubmed publisher
    ..However, both Hsl1p and Hsl7p are still required for Swe1p degradation, implying that these proteins play additional roles beyond localizing Swe1p to the neck. ..
  47. da Fonseca P, Kong E, Zhang Z, Schreiber A, Williams M, Morris E, et al. Structures of APC/C(Cdh1) with substrates identify Cdh1 and Apc10 as the D-box co-receptor. Nature. 2011;470:274-8 pubmed publisher
    ..Our results rationalize the contribution of both co-activator and core APC/C subunits to D-box recognition and provide a structural framework for understanding mechanisms of substrate recognition and catalysis by the APC/C. ..