Hi Advanced Cell Phys students at EC,
Please do the following:
See you on Monday. Amy
References:
School and University Projects page.
Instructions for Students.
Instructions for Faculty.
Copyrights.
Five Pillars.
Editing Policy.
Editing Cheat Sheet.
Tutorial.
I am working on the following:
Wee1 | |||||||
---|---|---|---|---|---|---|---|
Identifiers | |||||||
Symbol | Mitosis inhibitor protein kinase Wee1 | ||||||
Alt. symbols | wee1 dual specificity protein kinase Wee1 | ||||||
NCBI gene | 2539123 | ||||||
UniProt | P07527 | ||||||
Other data | |||||||
EC number | 2.7.11.1 | ||||||
|
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe (S. pombe). It has a molecular mass of 96 kDa and it is a key regulator of cell cycle progression. It influences cell size by inhibiting the entry into mitosis, through inhibiting Cdc2. It has homologues in many other organisms, including mammals.
The regulation of cell size is critical to ensure functionality of a cell. Besides environmental factors such as nutrients, growth factors and functional load, cell size is also controlled by a cellular cell size checkpoint.
Wee1 is a component of this checkpoint. It is a kinase determining the timepoint of entry into mitosis, thus influencing the size of the daughter cells. Loss of Wee1 function will produce smaller than normal daughter cell, because cell division occurs prematurely.
Its name is derived from the Scottish slang word wee, meaning small - its discoverer Paul Nurse was working at the University of Edinburgh in Scotland at the time of discovery. [1] [2]
Wee1 inhibits Cdc2 by phosphorylating it on two different sites, Tyr15 and Thr14 [3]. Cdc2 is crucial for the cyclin-dependent passage of the various cell cycle checkpoints. At least three checkpoints exist for which the inhibition of Cdc2 by Wee1 is important:
human WEE1 homolog (S. pombe) | |||||||
---|---|---|---|---|---|---|---|
Identifiers | |||||||
Symbol | WEE1 | ||||||
NCBI gene | 7465 | ||||||
HGNC | 12761 | ||||||
OMIM | 193525 | ||||||
RefSeq | NM_003390 | ||||||
UniProt | P30291 | ||||||
Other data | |||||||
Locus | Chr. 11 p15.3-15.1 | ||||||
|
human WEE1 homolog 2 (S. pombe) | |||||||
---|---|---|---|---|---|---|---|
Identifiers | |||||||
Symbol | WEE2 | ||||||
NCBI gene | 494551 | ||||||
HGNC | 19684 | ||||||
RefSeq | NM_001105558 | ||||||
UniProt | P0C1S8 | ||||||
Other data | |||||||
Locus | Chr. 7 q32-q32 | ||||||
|
The WEE1 gene has two known homologues in humans, WEE1 (also known as WEE1A) and WEE2 (WEE1B). The corresponding proteins are Wee1-like protein kinase and Wee1-like protein kinase 2 which act on the human Cdc2 homologue Cdk1.
The homologue to Wee1 in budding yeast Saccharomyces cerevisiae is called Swe1.
In S. pombe, Wee1 is phosphorylated
Cdc2 and
cyclin B make up the
maturation promoting factor (MPF) which promotes the entry into mitosis. It is inactivated by phosphorylation through Wee1 and activated by the phosphatase
Cdc25. Cdc25 in turn is activated by
Polo kinase and inactivated by
Chk1.
[5] Thus in S. pombe Wee1 regulation is mainly under the control of
phosphorylation.
[7]
[8]
[9]
[10]
At the G2/M transition, Cdc2 is activated by Cdc25 through dephosphorylation of Tyr15. At the same time, Wee1 is inactivated through phosphorylation at its C-terminal catalytic domain by Nim1/Cdr1. [9] Also, the active MPF will promote its own activity by activating Cdc25 and inactivating Wee1, creating a positive feedback loop, though this is not yet understood in detail. [5]
Higher eukaryotes regulate Wee1 via phosphorylation and degradation
In higher
eukaryotes, Wee1 inactivation occurs both by phosphorylation and
degradation.
[11]
The protein complex
[nb 1]
SCFβ-TrCP1/2 is an E3
ubiquitin ligase that functions in
Wee1A ubiquitination. The
M-phase kinases
Polo-like kinase (Plk1) and Cdc2 phosphorylate two serine residues in Wee1A which are recognized by SCFβ-TrCP1/2.
[12]
S. cerevisiae homologue Swe1
In
S. cerevisiae, cyclin-dependent kinase
Cdc28 (Cdc2 homologue) is phosphorylated by Swe1 (Wee1 homologue) and dephosphorylated by Mih1 (Cdc25 homologue). Nim1/Cdr1 homologue in S. cerevisiae, Hsl1, together with its related kinases Gin4 and Kcc4 localize Swe1 to the
bud-neck. Bud-neck associating kinases Cla4 and Cdc5 (polo kinase homologue) phosphorylate Swe1 at different stages of the cell cycle. Swe1 is also phosphorylated by Clb2-Cdc28 which serves as a recognition for further phosphorylation by Cdc5.
The S. cerevisiae protein Swe1 is also regulated by degradation. Swe1 is hyperphosphorylated by Clb2-Cdc28 and Cdc5 which may be a signal for ubiquitination and degradation by SCF E3 ubiquitin ligase complex as in higher eukaryotes. [13]
The mitosis promoting factor MPF also regulates DNA-damage induced apoptosis. Negative regulation of MPF by WEE1 causes aberrant mitosis and thus resistance to DNA-damage induced apoptosis. Kruppel-like factor 2 (KLF2) negatively regulates human WEE1, thus increasing sensitivity to DNA-damage induced apoptosis in cancer cells. [14]
Wee1 acts as a dosage-dependent inhibitor of mitosis. [15] Thus, the amount of Wee1 protein correlates with the size of the cells:
The fission yeast mutant wee1, also called wee1-, divides at a significantly smaller cell size than wildtype cells. Since Wee1 inhibits entry into mitosis, its absence will lead to division at a premature stage and sub-normal cell size. Conversely, when Wee1 expression is increased, mitosis is delayed and cells grow to a large size before dividing.
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Hi Advanced Cell Phys students at EC,
Please do the following:
See you on Monday. Amy
References:
School and University Projects page.
Instructions for Students.
Instructions for Faculty.
Copyrights.
Five Pillars.
Editing Policy.
Editing Cheat Sheet.
Tutorial.
I am working on the following:
Wee1 | |||||||
---|---|---|---|---|---|---|---|
Identifiers | |||||||
Symbol | Mitosis inhibitor protein kinase Wee1 | ||||||
Alt. symbols | wee1 dual specificity protein kinase Wee1 | ||||||
NCBI gene | 2539123 | ||||||
UniProt | P07527 | ||||||
Other data | |||||||
EC number | 2.7.11.1 | ||||||
|
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe (S. pombe). It has a molecular mass of 96 kDa and it is a key regulator of cell cycle progression. It influences cell size by inhibiting the entry into mitosis, through inhibiting Cdc2. It has homologues in many other organisms, including mammals.
The regulation of cell size is critical to ensure functionality of a cell. Besides environmental factors such as nutrients, growth factors and functional load, cell size is also controlled by a cellular cell size checkpoint.
Wee1 is a component of this checkpoint. It is a kinase determining the timepoint of entry into mitosis, thus influencing the size of the daughter cells. Loss of Wee1 function will produce smaller than normal daughter cell, because cell division occurs prematurely.
Its name is derived from the Scottish slang word wee, meaning small - its discoverer Paul Nurse was working at the University of Edinburgh in Scotland at the time of discovery. [1] [2]
Wee1 inhibits Cdc2 by phosphorylating it on two different sites, Tyr15 and Thr14 [3]. Cdc2 is crucial for the cyclin-dependent passage of the various cell cycle checkpoints. At least three checkpoints exist for which the inhibition of Cdc2 by Wee1 is important:
human WEE1 homolog (S. pombe) | |||||||
---|---|---|---|---|---|---|---|
Identifiers | |||||||
Symbol | WEE1 | ||||||
NCBI gene | 7465 | ||||||
HGNC | 12761 | ||||||
OMIM | 193525 | ||||||
RefSeq | NM_003390 | ||||||
UniProt | P30291 | ||||||
Other data | |||||||
Locus | Chr. 11 p15.3-15.1 | ||||||
|
human WEE1 homolog 2 (S. pombe) | |||||||
---|---|---|---|---|---|---|---|
Identifiers | |||||||
Symbol | WEE2 | ||||||
NCBI gene | 494551 | ||||||
HGNC | 19684 | ||||||
RefSeq | NM_001105558 | ||||||
UniProt | P0C1S8 | ||||||
Other data | |||||||
Locus | Chr. 7 q32-q32 | ||||||
|
The WEE1 gene has two known homologues in humans, WEE1 (also known as WEE1A) and WEE2 (WEE1B). The corresponding proteins are Wee1-like protein kinase and Wee1-like protein kinase 2 which act on the human Cdc2 homologue Cdk1.
The homologue to Wee1 in budding yeast Saccharomyces cerevisiae is called Swe1.
In S. pombe, Wee1 is phosphorylated
Cdc2 and
cyclin B make up the
maturation promoting factor (MPF) which promotes the entry into mitosis. It is inactivated by phosphorylation through Wee1 and activated by the phosphatase
Cdc25. Cdc25 in turn is activated by
Polo kinase and inactivated by
Chk1.
[5] Thus in S. pombe Wee1 regulation is mainly under the control of
phosphorylation.
[7]
[8]
[9]
[10]
At the G2/M transition, Cdc2 is activated by Cdc25 through dephosphorylation of Tyr15. At the same time, Wee1 is inactivated through phosphorylation at its C-terminal catalytic domain by Nim1/Cdr1. [9] Also, the active MPF will promote its own activity by activating Cdc25 and inactivating Wee1, creating a positive feedback loop, though this is not yet understood in detail. [5]
Higher eukaryotes regulate Wee1 via phosphorylation and degradation
In higher
eukaryotes, Wee1 inactivation occurs both by phosphorylation and
degradation.
[11]
The protein complex
[nb 1]
SCFβ-TrCP1/2 is an E3
ubiquitin ligase that functions in
Wee1A ubiquitination. The
M-phase kinases
Polo-like kinase (Plk1) and Cdc2 phosphorylate two serine residues in Wee1A which are recognized by SCFβ-TrCP1/2.
[12]
S. cerevisiae homologue Swe1
In
S. cerevisiae, cyclin-dependent kinase
Cdc28 (Cdc2 homologue) is phosphorylated by Swe1 (Wee1 homologue) and dephosphorylated by Mih1 (Cdc25 homologue). Nim1/Cdr1 homologue in S. cerevisiae, Hsl1, together with its related kinases Gin4 and Kcc4 localize Swe1 to the
bud-neck. Bud-neck associating kinases Cla4 and Cdc5 (polo kinase homologue) phosphorylate Swe1 at different stages of the cell cycle. Swe1 is also phosphorylated by Clb2-Cdc28 which serves as a recognition for further phosphorylation by Cdc5.
The S. cerevisiae protein Swe1 is also regulated by degradation. Swe1 is hyperphosphorylated by Clb2-Cdc28 and Cdc5 which may be a signal for ubiquitination and degradation by SCF E3 ubiquitin ligase complex as in higher eukaryotes. [13]
The mitosis promoting factor MPF also regulates DNA-damage induced apoptosis. Negative regulation of MPF by WEE1 causes aberrant mitosis and thus resistance to DNA-damage induced apoptosis. Kruppel-like factor 2 (KLF2) negatively regulates human WEE1, thus increasing sensitivity to DNA-damage induced apoptosis in cancer cells. [14]
Wee1 acts as a dosage-dependent inhibitor of mitosis. [15] Thus, the amount of Wee1 protein correlates with the size of the cells:
The fission yeast mutant wee1, also called wee1-, divides at a significantly smaller cell size than wildtype cells. Since Wee1 inhibits entry into mitosis, its absence will lead to division at a premature stage and sub-normal cell size. Conversely, when Wee1 expression is increased, mitosis is delayed and cells grow to a large size before dividing.
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