PEST motifs are not required for rapid calpain-mediated proteolysis of c-fos protein

Carillo, Serge; Pariat, Magali; Steff, Ann‐Muriel; Jariel-Encontre, Isabelle; Poulat, Françis; Berta, Philippe; Piechaczyk, Marc

doi:10.1042/bj3130245

Cited by 49 publications

(42 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This domain also acted as a transferable calpain susceptibility module. Other results do not support a function for PEST domains as calpain susceptibility motifs (39,40). Moreover, some calpain substrates lack strong PEST signatures (40 -42), whereas some PEST domain-containing proteins are either not susceptible or resistant to calpain (15,40).…”

Section: Discussionmentioning

confidence: 72%

Alternative Splice Variants of Doublecortin-like Kinase Are Differentially Expressed and Have Different Kinase Activities

Burgess

Reiner

2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

Alternative splicing of mRNA transcripts expands the range of protein products from a single gene locus. Several splice variants of DCLK (doublecortin-like kinase) have previously been reported. Here, we report the genomic organization underlying the splice variants of DCLK and examine the expression profile of two splice variants affecting the kinase domain of DCLK and CPG16 (candidate plasticity gene 16), one containing an Arg-rich domain and the other affecting the C terminus of the protein. These splice alternatives were differentially expressed in embryonic and adult brain. Both splice variants disrupted DCLK PEST domains; however, all splice variants remained sensitive to proteolysis by calpain. The adult-specific C-terminal splice variant of DCLK had reduced autophosphorylation activity, but similar kinase activity for myelin basic protein relative to the embryonic splice variant. The splice variant adding an Arg-rich domain gained an autophosphorylation site at Ser-382. Although this protein isoform was expressed mainly in the adult brain, the phosphorylated form was strongly enriched in embryonic brain and adult olfactory bulb, suggesting a possible role in migrating neurons.The majority of neuronal cells in the central nervous system are generated during embryogenesis and persist throughout life without further rounds of division and differentiation. Individual neurons accomplish an array of distinct tasks during their life span, including cellular migration, axon extension and pathfinding, synaptogenesis, and participation in mature nervous system function. It has been suggested that to deal with these diverse demands on cellular function, the repertoire of neuronal gene products is enhanced by alternative splicing and RNA editing. Following the description of differential RNA processing of the calcitonin gene (1), alternative splice forms of many gene products have been detected in the central nervous system (2, 3). Doublecortin-like kinase (DCLK) 1 is a serine-threonine kinase expressed in the central nervous system. The N-terminal domain of DCLK is very similar to the doublecortin protein and mediates microtubule localization (4 -6). The C-terminal kinase domain of DCLK resembles members of the family of calcium/calmodulin-dependent protein kinases, but lacks a canonical calmodulin-binding site (7). The human gene was named DCAMKL1 (doublecortin-and Ca 2ϩ /calmodulindependent protein kinase-like protein-1) (8); however, biochemical evidence does not indicate that calcium/calmodulin modulates kinase activity (7).The DCLK locus gives rise to several transcripts through differential splicing and use of alternative promoters (see Fig. 1). The DCL product includes the doublecortin domain, but lacks the kinase domain. DCLK Rϩ is a full-length transcript embracing both doublecortin and kinase domains and includes an additional 16 amino acids enriched in arginine residues (the Arg-rich domain), between the doublecortin and kinase domains (9). Two splice variants affecting the final coding exon of DCLK hav...

show abstract

Section: Discussionmentioning

confidence: 72%

Alternative Splice Variants of Doublecortin-like Kinase Are Differentially Expressed and Have Different Kinase Activities

Burgess

Reiner

2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Part of the PEST hypothesis proposed that, due to their intrinsic negative charges, PEST sequences might chelate calcium and, thereby, present their requested co-factor to calpains. However, biochemical and mutagenesis experiments (Carillo et al, 1996;Molinari et al, 1995) have unambiguously demonstrated no general requirement upon PEST motifs for proteolysis by calpains even though occasional interactions between calpains and substrates via PEST sequences have been described as exampli®ed in the case of IkBa (Shumway et al, 1999). Along the same line, the deletion of their PEST motifs do not detectably alter ubiquitin-dependent proteasomal degradation of proteins such as the RXRa nuclear receptor (Boudjelal et al, 2000) or the c-Myb protooncoprotein (Bies et al, 1999).…”

Section: Role Of Pest Sequences In Protein Degradationmentioning

confidence: 74%

Identification of a C-terminal tripeptide motif involved in the control of rapid proteasomal degradation of c-Fos proto-oncoprotein during the G0-to-S phase transition

et al. 2001

Self Cite

View full text Add to dashboard Cite

“…We believe that the degradation of cyclin F is independent of calpain ( Fig. 9), which is also the case for some other PEST-containing proteins (18,19).…”

Section: Fig 8 Cyclin F Is Not Ubiquitinated In Vivomentioning

confidence: 99%

“…The molecular basis of proteolysis of PEST-containing protein is far from clear. Proteolysis of several PEST-containing proteins involves the Ca 2ϩ -dependent protease calpain (16,17), whereas proteolysis of other PEST-containing proteins by calpain is shown to be independent of the PEST sequences (18,19).…”

mentioning

confidence: 99%

Cyclin F Is Degraded during G2-M by Mechanisms Fundamentally Different from Other Cyclins

Fung

Siu

Yam³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

Cyclin F, a cyclin that can form SCF complexes and bind to cyclin B, oscillates in the cell cycle with a pattern similar to cyclin A and cyclin B. Ectopic expression of cyclin F arrests the cell cycle in G 2 /M. How the level of cyclin F is regulated during the cell cycle is completely obscure. Here we show that, similar to cyclin A, cyclin F is degraded when the spindle assembly checkpoint is activated and accumulates when the DNA damage checkpoint is activated. Cyclin F is a very unstable protein throughout much of the cell cycle. Unlike other cyclins, degradation of cyclin F is independent of ubiquitination and proteasome-mediated pathways. Interestingly, proteolysis of cyclin F is likely to involve metalloproteases. Rapid destruction of cyclin F does not require the N-terminal F-box motif but requires the COOH-terminal PEST sequences. The PEST region alone is sufficient to interfere with the degradation of cyclin F and confer instability when fused to cyclin A. These data show that although cyclin F is degraded at similar time as the mitotic cyclins, the underlying mechanisms are entirely distinct.Cyclins and cyclin-dependent kinases (CDKs) 1 are key regulators of the eukaryotic cell cycle. In mammalian cells, different cyclin-CDK complexes are involved in regulating different cell cycle transitions: cyclin D-CDK4/6 for G 1 progression, cyclin E-CDK2 for the G 1 -S transition, cyclin A-CDK2 for S phase progression, and cyclin A/B-CDC2 for entry into M phase (1). Apart from these well known roles in the cell cycle, several cyclins and CDKs are involved in processes not directly related to the cell cycle. Cyclin D can bind and activate the estrogen receptor, and CDK5 is activated in postmitotic neurons by p35. The cyclin H-CDK7 complex is a component of both the CDKactivating kinase and the basal transcription factor TFIIH and can phosphorylate CDKs and the carboxyl-terminal repeat domain of the large subunit of RNA polymerase II, respectively.

show abstract

PEST motifs are not required for rapid calpain-mediated proteolysis of c-fos protein

Cited by 49 publications

References 44 publications

Alternative Splice Variants of Doublecortin-like Kinase Are Differentially Expressed and Have Different Kinase Activities

Alternative Splice Variants of Doublecortin-like Kinase Are Differentially Expressed and Have Different Kinase Activities

Identification of a C-terminal tripeptide motif involved in the control of rapid proteasomal degradation of c-Fos proto-oncoprotein during the G0-to-S phase transition

Cyclin F Is Degraded during G2-M by Mechanisms Fundamentally Different from Other Cyclins

Contact Info

Product

Resources

About