in mammalian cells, Cdt1 is targeted for degradation by the action of a protein complex that is recruited to the origin of replication by PCNA, the eukaryotic counterpart of the bacterial beta-clamp.

TLS Online TPP Program

#Id: 10017

#Unit 4. Cell Communication and Cell Signaling

In this complex, Ci becomes phosphorylated in a series of steps catalyzed by PKA, GSK3β, and CK1.

TLS Online TPP Program

#Id: 10018

#Unit 4. Cell Communication and Cell Signaling

The phosphorylated Ci is proteolytically cleaved by the ubiquitin-proteasome pathway, generating an N-terminal fragment Ci75, which functions as a transcriptional repressor of Hh target genes.

TLS Online TPP Program

#Id: 10019

#Unit 4. Cell Communication and Cell Signaling

Hh binds to Ptc, causing Ptc to be endocytosed from the cell surface and degraded, relieving the inhibition of Smo.

TLS Online TPP Program

#Id: 10020

#Unit 4. Cell Communication and Cell Signaling

The C-terminal segment of Smo binds Cos2, and Smo is stabilized from degradation

TLS Online TPP Program

#Id: 10021

#Unit 4. Cell Communication and Cell Signaling

Both Fu and Cos2 become extensively phosphorylated, and Fu-Cos2-Ci complex Dissociates

TLS Online TPP Program

#Id: 10022

#Unit 4. Cell Communication and Cell Signaling

Dissociation of cytosolic complex leads to the stabilization of the full-length Ci, which moves into the

nucleus, displaces the repressor Ci75 from the promoter of target genes, and induces expression of target genes.