Editing Proteasome (section)

===Apoptosis===
Both internal and external [[cell signaling|signals]] can lead to the induction of [[apoptosis]], or programmed cell death. The resulting deconstruction of cellular components is primarily carried out by specialized proteases known as [[caspase]]s, but the proteasome also plays important and diverse roles in the apoptotic process. The involvement of the proteasome in this process is indicated by both the increase in protein ubiquitination, and of E1, E2, and E3 enzymes that is observed well in advance of apoptosis.<ref name=autogenerated2>{{cite journal | vauthors = Haas AL, Baboshina O, Williams B, Schwartz LM | title = Coordinated induction of the ubiquitin conjugation pathway accompanies the developmentally programmed death of insect skeletal muscle | journal = The Journal of Biological Chemistry | volume = 270 | issue = 16 | pages = 9407–12 | date = April 1995 | pmid = 7721865 | doi = 10.1074/jbc.270.16.9407 | doi-access = free }}</ref><ref name="Schwartz">{{cite journal | vauthors = Schwartz LM, Myer A, Kosz L, Engelstein M, Maier C | title = Activation of polyubiquitin gene expression during developmentally programmed cell death | journal = Neuron | volume = 5 | issue = 4 | pages = 411–9 | date = October 1990 | pmid = 2169771 | doi = 10.1016/0896-6273(90)90080-Y | s2cid = 33829749 }}</ref><ref name="Low">{{cite journal | vauthors = Löw P, Bussell K, Dawson SP, Billett MA, Mayer RJ, Reynolds SE | title = Expression of a 26S proteasome ATPase subunit, MS73, in muscles that undergo developmentally programmed cell death, and its control by ecdysteroid hormones in the insect Manduca sexta | journal = FEBS Letters | volume = 400 | issue = 3 | pages = 345–9 | date = January 1997 | pmid = 9009228 | doi = 10.1016/S0014-5793(96)01413-5 | s2cid = 10873052 | doi-access = free | bibcode = 1997FEBSL.400..345L }}</ref> During apoptosis, proteasomes localized to the nucleus have also been observed to translocate to outer membrane [[blebbing|blebs]] characteristic of apoptosis.<ref name="Pitzer">{{cite journal | vauthors = Pitzer F, Dantes A, Fuchs T, Baumeister W, Amsterdam A | title = Removal of proteasomes from the nucleus and their accumulation in apoptotic blebs during programmed cell death | journal = FEBS Letters | volume = 394 | issue = 1 | pages = 47–50 | date = September 1996 | pmid = 8925925 | doi = 10.1016/0014-5793(96)00920-9 | bibcode = 1996FEBSL.394...47P | s2cid = 29256092 }}</ref>

Proteasome inhibition has different effects on apoptosis induction in different cell types. In general, the proteasome is not required for apoptosis, although inhibiting it is pro-apoptotic in most cell types that have been studied. Apoptosis is mediated through disrupting the regulated degradation of pro-growth cell cycle proteins.<ref name="Adams"/> However, some cell lines&nbsp;— in particular, [[primary culture]]s of [[G0 phase|quiescent]] and [[cell differentiation|differentiated]] cells such as [[thymocyte]]s and [[neuron]]s&nbsp;— are prevented from undergoing apoptosis on exposure to proteasome inhibitors. The mechanism for this effect is not clear, but is hypothesized to be specific to cells in quiescent states, or to result from the differential activity of the pro-apoptotic [[kinase]] [[JNK]].<ref name="Orlowski">{{cite journal | vauthors = Orlowski RZ | title = The role of the ubiquitin-proteasome pathway in apoptosis | journal = Cell Death and Differentiation | volume = 6 | issue = 4 | pages = 303–13 | date = April 1999 | pmid = 10381632 | doi = 10.1038/sj.cdd.4400505 | doi-access = free }}</ref> The ability of proteasome inhibitors to induce apoptosis in rapidly dividing cells has been exploited in several recently developed [[chemotherapy]] agents such as [[bortezomib]] and {{nowrap|[[salinosporamide A]]}}.