- Email: [email protected]
BZR1 Degradation to Decode Distinct Developmental and Environmental Cues in Plants
Accepted Manuscript Multiple ways of BES1/BZR1 degradation to decode distinct developmental and environmental cues in plants Mengran Yang, Xuelu Wang
PII: DOI: Reference:
S1674-2052(17)30171-5 10.1016/j.molp.2017.06.005 MOLP 477
To appear in: MOLECULAR PLANT Accepted Date: 13 June 2017
Please cite this article as: Yang M., and Wang X. (2017). Multiple ways of BES1/BZR1 degradation to decode distinct developmental and environmental cues in plants. Mol. Plant. doi: 10.1016/ j.molp.2017.06.005. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. All studies published in MOLECULAR PLANT are embargoed until 3PM ET of the day they are published as corrected proofs on-line. Studies cannot be publicized as accepted manuscripts or uncorrected proofs.
ACCEPTED MANUSCRIPT Multiple ways of BES1/BZR1 degradation to decode distinct developmental and environmental cues in plants
1
Center of Integrative Biology, College of Life Science and Technology, Huazhong
Agricultural University, Wuhan 430070, China 2
RI PT
Mengran Yang1, 2 and Xuelu Wang1, *
State Key Laboratory of Genetic Engineering, Department of Genetics, School of
SC
Life Sciences, Fudan University, Shanghai 200438, China
AC C
EP
TE D
M AN U
*Correspondence: Xuelu Wang ([email protected])
1
ACCEPTED MANUSCRIPT Plants must constantly integrate various environment stimuli and many endogenous hormones to optimize their growth and development. BRI1-EMS-SUPPRESSOR 1 (BES1) and BRASSINAZOLE RESISTANT 1 (BZR1) act not only as key transcription factors in brassinosteroid (BR) signaling pathway, but also as a hub that
RI PT
integrates diverse signals to regulate plant development and environment adaptability (Wang et al., 2014). Both BES1 and BZR1 were identified through forward genetic
screens of mutants with constitutively activated BR signaling. The gain-of-function bes1-D and bzr1-D mutants exhibit constitutive BR responses, and the bes1-D and
SC
bzr1-D proteins show significantly increased stability as compared with the wild-type BES1 and BZR1, respectively (He et al., 2002; Yin et al., 2002), indicating that the
M AN U
stability of BES1/BZR1 is critical for their function. However, in more than a decade after the identification of BES1/BZR1, only limited information is available to explain how BES1/BZR1 stability is regulated. It's known that the phosphorylation status of BES1/BZR1 is rapidly changed in responding to BRs, which has been widely used to determine the BR signaling outputs. The BRASSINOSTEROID INSENSITIVE 2
TE D
(BIN2) kinase phosphorylates and inhibits the activity of BES1/BZR1 (He et al., 2002; Yin et al., 2002), whereas the protein phosphatase 2A (PP2A) dephosphorylates and activates BES1/BZR1 (Tang et al., 2011). It has long been assumed that the
EP
degradation of BES1/BZR1 is mainly dependent on their phosphorylation and through the 26S proteasome (He et al., 2002; Yin et al., 2002), but several recent studies demonstrated that the regulation of BES1/BZR1 stability is more diverse and far more
AC C
complicated than what we thought before. In 2013, Wang et al. reported a direct BES1-degradation mechanism, in which
BES1 serves as the substrate of MORE AXILLARY GROWTH LOCUS 2 (MAX2), an F-box protein critical for strigolactone (SL) signaling, to regulate shoot branching in Arabidopsis (Figure 1, left). It was found that the bes1-D mutant has increased branch number and is insensitive to SLs. BES1 and its homologs directly interact with MAX2 and are ubiquitinated and degraded by MAX2, a subunit of the Skp-CULLIN-F-box (SCF) E3 ubiquitin ligase complex. Meanwhile, the
2
ACCEPTED MANUSCRIPT MAX2-mediated BES1 degradation is promoted by SL treatment (Wang et al., 2013). Furthermore, genetic data showed that knockdown of BES1 and its homologs suppressed the branching phenotype of max2-1, suggesting that BES1 is essential for SL-controlled branching in the downstream of MAX2 (Wang et al., 2013).
RI PT
Interestingly, both phosphorylated and dephosphorylated BES1 can interact with and be degraded by MAX2. Thus, the MAX2-mediated tissue-specific (xylem
parenchyma cells) degradation of BES1 controls a distinct developmental process, shoot branching, from the ubiquitously present BR signaling pathway. Although a
SC
recent report claimed that BES1 is not involved in SL-regulated shoot branching
(Bennett et al., 2016), because the bes1-D/Col-0 mutant they used was constructed
M AN U
through backcrossing bes1-D of En2 background into the Col-0 wild type, the background of bes1-D/Col-0 and Col-0 is not identical. In addition, the bes1-1 mutant they used is only a T-DNA knockout of BES1 but not their homologues, it is normal this BES1 T-DNA lines showed a wild-type phenotype of branching. Two recent studies revealed that BES1/BZR1 degradation is also mediated by
TE D
two other types of E3 ligases, CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) and SINA of Arabidopsis thaliana (SINATs), which are involved in light/dark-mediated plant growth (Kim et al., 2014; Yang et al., 2017) (Figure 1,
EP
middle). Kim et al. (2014) showed that the dark-activated ubiquitin ligase COP1 interacts with and degrades the phosphorylated (inactive) BZR1. They found that the
AC C
dark treatment reduced the amount of the phosphorylated BZR1, leading to an increased ratio of the dephosphorylated to the phosphorylated BZR1 to enhance BR signaling and hypocotyl elongation (Kim et al., 2014). They proposed a dark-dependent degradation mechanism of the phosphorylated BZR1, whereas whether the stability of the more active and dephosphorylated form of BES1/BZR1 can be regulated by the 26S proteasome pathway remains unclear until this year. Recently, Yang et al. (2017) identified a family of RING figure E3 ligase, SINATs, which prefer to target the dephosphorylated BES1 for degradation in the light. SINATs directly interact with the dephosphorylated BES1/BZR1 and function as the
3
ACCEPTED MANUSCRIPT E3 ligases to mediate BES1 ubiquitination and subsequent degradation through the 26S proteasome pathway. Genetic analyses demonstrated that SINATs inhibit BR signaling and plant growth in a BES1-dependent manner, as BES1-RNAi counteracted the BR-enhanced phenotypes of the SINATs-RNAi lines. Interestingly, they found that
RI PT
the protein levels of SINATs were decreased in the dark but increased in the light, leading to changes of the dephosphorylated BES1 level accordingly. Thus, the SINATs-mediated BES1 degradation participates in BR signaling output and
light-mediated regulation of plant growth (Yang et al., 2017). These two studies led to
SC
a model that dark and light differentially regulate the stability of the phosphorylated
and dephosphorylated BES1/BZR1, respectively, through distinct E3 ubiquitin ligases
M AN U
to control plant growth and development (Kim et al., 2014; Yang et al., 2017) (Figure 1, middle).
In addition to being degraded though proteasome pathway, two recent reports indicate that BES1/BZR1 can also be targeted for autophagy-mediated degradation to coordinate plant growth and stress responses (Nolan et al., 2017; Zhang et al., 2016)
TE D
(Figure 1, right). Zhang et al. (2016) showed that sugar signaling promotes the accumulation of BZR1 through TARGET OF RAPAMYCIN (TOR) pathway to promote plant growth, but sugar starvation-triggered TOR inactivation leads to
EP
autophagy-mediated BZR1 degradation for balancing growth with carbon availability in Arabidopsis. However, the detailed mechanism underlying the process of
AC C
autophagy-mediated degradation of BES1/BZR1 remains to be established. As the inhibitors of autophagy pathway could also cause significant accumulation of BES1, similar to the inhibitor of proteasome pathway, Nolan et al., (2017) attempted to answer how BES1 was degraded by the autophagy pathway. They identified the DSK2, which is an ubiquitin-binding receptor in Arabidopsis, as an interacting protein of BES1, and further demonstrated that DSK2 mediates the autophagy-associated degradation of BES1 through interacting with ATG8, which is an ubiquitin-like protein directing autophagosome formation, under stressful conditions (Nolan et al., 2017). Furthermore, they found that BIN2 could phosphorylate DSK2 to promote its
4
ACCEPTED MANUSCRIPT interaction with ATG8 and facilitate BES1 degradation. The DSK2-RNAi plants showed the impaired BES1 degradation and compromised drought and starvation stress responses. In addition, they found the SINAT E3 ligases are also involved in BES1 degradation during starvation stress (Nolan et al., 2017) (Figure 1, right).
RI PT
In summary, BES1/BZR1 could be degraded through distinct E3 ubiquitin ligases in tissue-specific developmental processes and under diverse hormonal and environmental conditions, and both proteasome and autophagy pathways play
important roles in mediating their degradation. The distinct BES1/BZR1-E3 modules
SC
serve as decoders of various upstream signals to ensure proper plant development and environmental adaptation (Figure 1). Despite the above-mentioned findings, some
M AN U
questions remain to be further studied: (1) Whether and how does BR signaling directly affect the degradation of BES1/BZR1 under diverse environmental conditions? (2) Does the phosphorylated BES1/BZR1 have specific function in plant development? (3) How do plants optimally balance their growth and stress response by fine-tuning the degradation of different forms of BES1/BZR1? Answers to these questions would
TE D
deepen our understanding of multifaceted roles of BES1/BZR1 in optimizing plant growth and development under changing environments and may provide new
FUNDING
EP
strategies and targets for crop improvement.
This work in the authors' laboratory was supported by grant 2015CB910200 of the
AC C
National Key Basic Research Foundation of China, grants 31430046, 91535104, and 31271300 (to X.W.) of the National Natural Science Foundation of China, and initiative grants 2662015PY020 and 2014RC002 of Huazhong Agricultural University (to X. W.).
ACKNOWLEDGMENTS We apologize for not citing all the relevant references due to space limitations. No conflict of interest declared. REFERENCE: Bennett, T., Liang, Y.Y., Seale, M., Ward, S., Muller, D., and Leyser, O. (2016). 5
ACCEPTED MANUSCRIPT Strigolactone regulates shoot development through a core signaling pathway. Biol. Open 5:1806-1820. He, J.X., Gendron, J.M., Yang, Y.L., Li, J.M., and Wang, Z.Y. (2002). The GSK3-like kinase BIN2 phosphorylates and destabilizes BZR1, a positive regulator of the
RI PT
brassinosteroid signaling pathway in Arabidopsis. Proc. Natl. Acad. Sci. USA 99:10185-10190.
Kim, B., Jeong, Y.J., Corvalan, C., Fujioka, S., Cho, S., Park, T., and Choe, S. (2014). Darkness and gulliver2/phyB mutation decrease the abundance of
SC
phosphorylated BZR1 to activate brassinosteroid signaling in Arabidopsis. Plant J. 77:737-747.
M AN U
Nolan, T.M., Brennan, B., Yang, M.R., Chen, J.N., Zhang, M.C., Li, Z.H., Wang, X.L., Bassham, D.C., Walley, J., and Yin, Y.H. (2017). Selective Autophagy of BES1 Mediated by DSK2 Balances Plant Growth and Survival. Dev. Cell 41:33-46.
Tang, W.Q., Yuan, M., Wang, R.J., Yang, Y.H., Wang, C.M., Oses-Prieto, J.A., Kim,
TE D
T.W., Zhou, H.W., Deng, Z.P., Gampala, S.S., et al. (2011). PP2A activates brassinosteroid-responsive gene expression and plant growth by dephosphorylating BZR1. Nat. Cell. Biol. 13:124-131.
EP
Wang, W.F., Bai, M.Y., and Wang, Z.Y. (2014). The brassinosteroid signaling network-a paradigm of signal integration. Curr. Opin. Plant Biol. 21:147-153. Wang, Y., Sun, S.Y., Zhu, W.J., Jia, K.P., Yang, H.Q., and Wang, X.L. (2013).
AC C
Strigolactone/MAX2-induced degradation of brassinosteroid transcriptional
effector BES1 regulates shoot branching. Dev. Cell 27:681-688.
Yang, M.R., Li, C.X., Cai, Z.Y., Hu, Y.M., Nolan, T., Yu, F.F., Yin, Y.H., Xie, Q., Tang, G.L., and Wang, X.L. (2017) SINAT E3 ligases control the light-mediated
stability of the brassinosteroid-activated transcription factor BES1 in Arabidopsis. Dev. Cell, 41:47-58. Yin, Y.H., Wang, Z.-Y., Mora-Garcia, S., Li, J.M., Yoshida, S., Asami, T., and Chory, J. (2002). BES1 Accumulates in the Nucleus in Response to Brassinosteroids to Regulate Gene Expression and Promote Stem Elongation. Cell 109:181-191. 6
ACCEPTED MANUSCRIPT Zhang, Z.Z., Zhu, J.Y., Roh, J., Marchive, C., Kim, S.K., Meyer, C., Sun, Y., Wang, W.F., and Wang, Z.Y. (2016). TOR Signaling Promotes Accumulation of BZR1 to Balance Growth with Carbon Availability in Arabidopsis. Curr. Biol.
AC C
EP
TE D
M AN U
SC
RI PT
26:1854.
7
ACCEPTED MANUSCRIPT FIGURE LEGEND Figure 1. BES1/BZR1 are degraded through different ways in response to various developmental and environmental signals. In response to endogenous or exogenous stimuli, the protein stability of BES1/BZR1
RI PT
are precisely regulated. The module of manipulating BES1/BZR1 protein level serve as decoder that links the input signals and output physiological responses. Left: Strigolactones (SLs) promote the MAX2-mediated degradation of both
phosphorylated and dephosphorylated BES1/BZR1 to inhibit shoot branching. Middle:
SC
SINATs specifically mediate the degradation of the dephosphorylated BES1/BZR1 in the light to inhibit hypocotyl elongation, whereas COP1 mediates the degradation of
M AN U
the phosphorylated BES1/BZR1 in the dark, leading to the accumulation of dephosphorylated BES1/ BZR1 for hypocotyl elongation. Right: BES1/BZR1 are targeted to autophagy through interating with DSK2 under drought or starvation conditions to balance plant growth and survival. BIN2 phosphorylates DSK2 and promote its interation with ATG8 to enhance autophagy-associated degradation of
TE D
BES1/BZR1. In addition, sugar signaling inhibits the autophagy-mediated
AC C
EP
degradation of BES1/BZR1 through the TOR pathway to promote plant growth.
8
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
PII: DOI: Reference:
S1674-2052(17)30171-5 10.1016/j.molp.2017.06.005 MOLP 477
To appear in: MOLECULAR PLANT Accepted Date: 13 June 2017
Please cite this article as: Yang M., and Wang X. (2017). Multiple ways of BES1/BZR1 degradation to decode distinct developmental and environmental cues in plants. Mol. Plant. doi: 10.1016/ j.molp.2017.06.005. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. All studies published in MOLECULAR PLANT are embargoed until 3PM ET of the day they are published as corrected proofs on-line. Studies cannot be publicized as accepted manuscripts or uncorrected proofs.
ACCEPTED MANUSCRIPT Multiple ways of BES1/BZR1 degradation to decode distinct developmental and environmental cues in plants
1
Center of Integrative Biology, College of Life Science and Technology, Huazhong
Agricultural University, Wuhan 430070, China 2
RI PT
Mengran Yang1, 2 and Xuelu Wang1, *
State Key Laboratory of Genetic Engineering, Department of Genetics, School of
SC
Life Sciences, Fudan University, Shanghai 200438, China
AC C
EP
TE D
M AN U
*Correspondence: Xuelu Wang ([email protected])
1
ACCEPTED MANUSCRIPT Plants must constantly integrate various environment stimuli and many endogenous hormones to optimize their growth and development. BRI1-EMS-SUPPRESSOR 1 (BES1) and BRASSINAZOLE RESISTANT 1 (BZR1) act not only as key transcription factors in brassinosteroid (BR) signaling pathway, but also as a hub that
RI PT
integrates diverse signals to regulate plant development and environment adaptability (Wang et al., 2014). Both BES1 and BZR1 were identified through forward genetic
screens of mutants with constitutively activated BR signaling. The gain-of-function bes1-D and bzr1-D mutants exhibit constitutive BR responses, and the bes1-D and
SC
bzr1-D proteins show significantly increased stability as compared with the wild-type BES1 and BZR1, respectively (He et al., 2002; Yin et al., 2002), indicating that the
M AN U
stability of BES1/BZR1 is critical for their function. However, in more than a decade after the identification of BES1/BZR1, only limited information is available to explain how BES1/BZR1 stability is regulated. It's known that the phosphorylation status of BES1/BZR1 is rapidly changed in responding to BRs, which has been widely used to determine the BR signaling outputs. The BRASSINOSTEROID INSENSITIVE 2
TE D
(BIN2) kinase phosphorylates and inhibits the activity of BES1/BZR1 (He et al., 2002; Yin et al., 2002), whereas the protein phosphatase 2A (PP2A) dephosphorylates and activates BES1/BZR1 (Tang et al., 2011). It has long been assumed that the
EP
degradation of BES1/BZR1 is mainly dependent on their phosphorylation and through the 26S proteasome (He et al., 2002; Yin et al., 2002), but several recent studies demonstrated that the regulation of BES1/BZR1 stability is more diverse and far more
AC C
complicated than what we thought before. In 2013, Wang et al. reported a direct BES1-degradation mechanism, in which
BES1 serves as the substrate of MORE AXILLARY GROWTH LOCUS 2 (MAX2), an F-box protein critical for strigolactone (SL) signaling, to regulate shoot branching in Arabidopsis (Figure 1, left). It was found that the bes1-D mutant has increased branch number and is insensitive to SLs. BES1 and its homologs directly interact with MAX2 and are ubiquitinated and degraded by MAX2, a subunit of the Skp-CULLIN-F-box (SCF) E3 ubiquitin ligase complex. Meanwhile, the
2
ACCEPTED MANUSCRIPT MAX2-mediated BES1 degradation is promoted by SL treatment (Wang et al., 2013). Furthermore, genetic data showed that knockdown of BES1 and its homologs suppressed the branching phenotype of max2-1, suggesting that BES1 is essential for SL-controlled branching in the downstream of MAX2 (Wang et al., 2013).
RI PT
Interestingly, both phosphorylated and dephosphorylated BES1 can interact with and be degraded by MAX2. Thus, the MAX2-mediated tissue-specific (xylem
parenchyma cells) degradation of BES1 controls a distinct developmental process, shoot branching, from the ubiquitously present BR signaling pathway. Although a
SC
recent report claimed that BES1 is not involved in SL-regulated shoot branching
(Bennett et al., 2016), because the bes1-D/Col-0 mutant they used was constructed
M AN U
through backcrossing bes1-D of En2 background into the Col-0 wild type, the background of bes1-D/Col-0 and Col-0 is not identical. In addition, the bes1-1 mutant they used is only a T-DNA knockout of BES1 but not their homologues, it is normal this BES1 T-DNA lines showed a wild-type phenotype of branching. Two recent studies revealed that BES1/BZR1 degradation is also mediated by
TE D
two other types of E3 ligases, CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) and SINA of Arabidopsis thaliana (SINATs), which are involved in light/dark-mediated plant growth (Kim et al., 2014; Yang et al., 2017) (Figure 1,
EP
middle). Kim et al. (2014) showed that the dark-activated ubiquitin ligase COP1 interacts with and degrades the phosphorylated (inactive) BZR1. They found that the
AC C
dark treatment reduced the amount of the phosphorylated BZR1, leading to an increased ratio of the dephosphorylated to the phosphorylated BZR1 to enhance BR signaling and hypocotyl elongation (Kim et al., 2014). They proposed a dark-dependent degradation mechanism of the phosphorylated BZR1, whereas whether the stability of the more active and dephosphorylated form of BES1/BZR1 can be regulated by the 26S proteasome pathway remains unclear until this year. Recently, Yang et al. (2017) identified a family of RING figure E3 ligase, SINATs, which prefer to target the dephosphorylated BES1 for degradation in the light. SINATs directly interact with the dephosphorylated BES1/BZR1 and function as the
3
ACCEPTED MANUSCRIPT E3 ligases to mediate BES1 ubiquitination and subsequent degradation through the 26S proteasome pathway. Genetic analyses demonstrated that SINATs inhibit BR signaling and plant growth in a BES1-dependent manner, as BES1-RNAi counteracted the BR-enhanced phenotypes of the SINATs-RNAi lines. Interestingly, they found that
RI PT
the protein levels of SINATs were decreased in the dark but increased in the light, leading to changes of the dephosphorylated BES1 level accordingly. Thus, the SINATs-mediated BES1 degradation participates in BR signaling output and
light-mediated regulation of plant growth (Yang et al., 2017). These two studies led to
SC
a model that dark and light differentially regulate the stability of the phosphorylated
and dephosphorylated BES1/BZR1, respectively, through distinct E3 ubiquitin ligases
M AN U
to control plant growth and development (Kim et al., 2014; Yang et al., 2017) (Figure 1, middle).
In addition to being degraded though proteasome pathway, two recent reports indicate that BES1/BZR1 can also be targeted for autophagy-mediated degradation to coordinate plant growth and stress responses (Nolan et al., 2017; Zhang et al., 2016)
TE D
(Figure 1, right). Zhang et al. (2016) showed that sugar signaling promotes the accumulation of BZR1 through TARGET OF RAPAMYCIN (TOR) pathway to promote plant growth, but sugar starvation-triggered TOR inactivation leads to
EP
autophagy-mediated BZR1 degradation for balancing growth with carbon availability in Arabidopsis. However, the detailed mechanism underlying the process of
AC C
autophagy-mediated degradation of BES1/BZR1 remains to be established. As the inhibitors of autophagy pathway could also cause significant accumulation of BES1, similar to the inhibitor of proteasome pathway, Nolan et al., (2017) attempted to answer how BES1 was degraded by the autophagy pathway. They identified the DSK2, which is an ubiquitin-binding receptor in Arabidopsis, as an interacting protein of BES1, and further demonstrated that DSK2 mediates the autophagy-associated degradation of BES1 through interacting with ATG8, which is an ubiquitin-like protein directing autophagosome formation, under stressful conditions (Nolan et al., 2017). Furthermore, they found that BIN2 could phosphorylate DSK2 to promote its
4
ACCEPTED MANUSCRIPT interaction with ATG8 and facilitate BES1 degradation. The DSK2-RNAi plants showed the impaired BES1 degradation and compromised drought and starvation stress responses. In addition, they found the SINAT E3 ligases are also involved in BES1 degradation during starvation stress (Nolan et al., 2017) (Figure 1, right).
RI PT
In summary, BES1/BZR1 could be degraded through distinct E3 ubiquitin ligases in tissue-specific developmental processes and under diverse hormonal and environmental conditions, and both proteasome and autophagy pathways play
important roles in mediating their degradation. The distinct BES1/BZR1-E3 modules
SC
serve as decoders of various upstream signals to ensure proper plant development and environmental adaptation (Figure 1). Despite the above-mentioned findings, some
M AN U
questions remain to be further studied: (1) Whether and how does BR signaling directly affect the degradation of BES1/BZR1 under diverse environmental conditions? (2) Does the phosphorylated BES1/BZR1 have specific function in plant development? (3) How do plants optimally balance their growth and stress response by fine-tuning the degradation of different forms of BES1/BZR1? Answers to these questions would
TE D
deepen our understanding of multifaceted roles of BES1/BZR1 in optimizing plant growth and development under changing environments and may provide new
FUNDING
EP
strategies and targets for crop improvement.
This work in the authors' laboratory was supported by grant 2015CB910200 of the
AC C
National Key Basic Research Foundation of China, grants 31430046, 91535104, and 31271300 (to X.W.) of the National Natural Science Foundation of China, and initiative grants 2662015PY020 and 2014RC002 of Huazhong Agricultural University (to X. W.).
ACKNOWLEDGMENTS We apologize for not citing all the relevant references due to space limitations. No conflict of interest declared. REFERENCE: Bennett, T., Liang, Y.Y., Seale, M., Ward, S., Muller, D., and Leyser, O. (2016). 5
ACCEPTED MANUSCRIPT Strigolactone regulates shoot development through a core signaling pathway. Biol. Open 5:1806-1820. He, J.X., Gendron, J.M., Yang, Y.L., Li, J.M., and Wang, Z.Y. (2002). The GSK3-like kinase BIN2 phosphorylates and destabilizes BZR1, a positive regulator of the
RI PT
brassinosteroid signaling pathway in Arabidopsis. Proc. Natl. Acad. Sci. USA 99:10185-10190.
Kim, B., Jeong, Y.J., Corvalan, C., Fujioka, S., Cho, S., Park, T., and Choe, S. (2014). Darkness and gulliver2/phyB mutation decrease the abundance of
SC
phosphorylated BZR1 to activate brassinosteroid signaling in Arabidopsis. Plant J. 77:737-747.
M AN U
Nolan, T.M., Brennan, B., Yang, M.R., Chen, J.N., Zhang, M.C., Li, Z.H., Wang, X.L., Bassham, D.C., Walley, J., and Yin, Y.H. (2017). Selective Autophagy of BES1 Mediated by DSK2 Balances Plant Growth and Survival. Dev. Cell 41:33-46.
Tang, W.Q., Yuan, M., Wang, R.J., Yang, Y.H., Wang, C.M., Oses-Prieto, J.A., Kim,
TE D
T.W., Zhou, H.W., Deng, Z.P., Gampala, S.S., et al. (2011). PP2A activates brassinosteroid-responsive gene expression and plant growth by dephosphorylating BZR1. Nat. Cell. Biol. 13:124-131.
EP
Wang, W.F., Bai, M.Y., and Wang, Z.Y. (2014). The brassinosteroid signaling network-a paradigm of signal integration. Curr. Opin. Plant Biol. 21:147-153. Wang, Y., Sun, S.Y., Zhu, W.J., Jia, K.P., Yang, H.Q., and Wang, X.L. (2013).
AC C
Strigolactone/MAX2-induced degradation of brassinosteroid transcriptional
effector BES1 regulates shoot branching. Dev. Cell 27:681-688.
Yang, M.R., Li, C.X., Cai, Z.Y., Hu, Y.M., Nolan, T., Yu, F.F., Yin, Y.H., Xie, Q., Tang, G.L., and Wang, X.L. (2017) SINAT E3 ligases control the light-mediated
stability of the brassinosteroid-activated transcription factor BES1 in Arabidopsis. Dev. Cell, 41:47-58. Yin, Y.H., Wang, Z.-Y., Mora-Garcia, S., Li, J.M., Yoshida, S., Asami, T., and Chory, J. (2002). BES1 Accumulates in the Nucleus in Response to Brassinosteroids to Regulate Gene Expression and Promote Stem Elongation. Cell 109:181-191. 6
ACCEPTED MANUSCRIPT Zhang, Z.Z., Zhu, J.Y., Roh, J., Marchive, C., Kim, S.K., Meyer, C., Sun, Y., Wang, W.F., and Wang, Z.Y. (2016). TOR Signaling Promotes Accumulation of BZR1 to Balance Growth with Carbon Availability in Arabidopsis. Curr. Biol.
AC C
EP
TE D
M AN U
SC
RI PT
26:1854.
7
ACCEPTED MANUSCRIPT FIGURE LEGEND Figure 1. BES1/BZR1 are degraded through different ways in response to various developmental and environmental signals. In response to endogenous or exogenous stimuli, the protein stability of BES1/BZR1
RI PT
are precisely regulated. The module of manipulating BES1/BZR1 protein level serve as decoder that links the input signals and output physiological responses. Left: Strigolactones (SLs) promote the MAX2-mediated degradation of both
phosphorylated and dephosphorylated BES1/BZR1 to inhibit shoot branching. Middle:
SC
SINATs specifically mediate the degradation of the dephosphorylated BES1/BZR1 in the light to inhibit hypocotyl elongation, whereas COP1 mediates the degradation of
M AN U
the phosphorylated BES1/BZR1 in the dark, leading to the accumulation of dephosphorylated BES1/ BZR1 for hypocotyl elongation. Right: BES1/BZR1 are targeted to autophagy through interating with DSK2 under drought or starvation conditions to balance plant growth and survival. BIN2 phosphorylates DSK2 and promote its interation with ATG8 to enhance autophagy-associated degradation of
TE D
BES1/BZR1. In addition, sugar signaling inhibits the autophagy-mediated
AC C
EP
degradation of BES1/BZR1 through the TOR pathway to promote plant growth.
8
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT