Endoplasmic Reticulum Stress Induces Myostatin High Molecular Weight Aggregates and Impairs Mature Myostatin Secretion

The type II iodothyronine deiodinase (D2) is a type I endoplasmic reticulum (ER)-resident thioredoxin fold-containing selenoprotein that activates thyroid hormone. D2 is inactivated by ER-associated ubiquitination and can be reactivated by two ubiquitin-specific peptidase-class D2-interacting deubiquitinases (DUBs). Here, we used D2-expressing cell models to define that D2 ubiquitination (UbD2) occurs via K48-linked ubiquitin chains and that exposure to its natural substrate, T4, accelerates UbD2 formation and retrotranslocation to the cytoplasm via interaction with the p97-ATPase complex. D2 retrotranslocation also includes deubiquitination by the p97-associated DUB Ataxin-3 (Atx3). Inhibiting Atx3 with eeyarestatin-I did not affect D2:p97 binding but decreased UbD2 retrotranslocation and caused ER accumulation of high-molecular weight UbD2 bands possibly by interfering with the D2-ubiquitin-specific peptidases binding. Once in the cytosol, D2 is delivered to the proteasomes as evidenced by coprecipitation with 19S proteasome subunit S5a and increased colocalization with the 20S proteasome. We conclude that interaction between UbD2 and p97/Atx3 mediates retranslocation of UbD2 to the cytoplasm for terminal degradation in the proteasomes, a pathway that is accelerated by exposure to T4.

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Secretion of a low‐molecular‐weight species of endogenous GRP94 devoid of the KDEL motif during endoplasmic reticulum stress in Chinese hamster ovary cells

Traffic ◽

10.1111/tra.12818 ◽

2021 ◽

Author(s):

Andrew Samy ◽

Noriko Yamano‐Adachi ◽

Yuichi Koga ◽

Takeshi Omasa

Keyword(s):

Molecular Weight ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Chinese Hamster Ovary ◽

Chinese Hamster Ovary Cells ◽

Chinese Hamster ◽

Low Molecular Weight ◽

Ovary Cells

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A high-molecular-weight complex of membrane proteins BAP29/BAP31 is involved in the retention of membrane-bound IgD in the endoplasmic reticulum

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1633363100 ◽

2003 ◽

Vol 100 (17) ◽

pp. 9861-9866 ◽

Cited By ~ 63

Author(s):

W. W. A. Schamel ◽

S. Kuppig ◽

B. Becker ◽

K. Gimborn ◽

H.-P. Hauri ◽

...

Keyword(s):

Molecular Weight ◽

Endoplasmic Reticulum ◽

Membrane Proteins ◽

High Molecular Weight ◽

High Molecular Weight Complex ◽

Membrane Bound

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Paracrystalline inclusions within the cisternae of rough endoplasmic reticulum in a pleomorphic sarcoma: A marker of fibroblastic differentiation?

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100168992 ◽

1994 ◽

Vol 52 ◽

pp. 252-253

Author(s):

W.T. Gunning ◽

K. Hameed ◽

E.P. Calomeni

Keyword(s):

Molecular Weight ◽

Endoplasmic Reticulum ◽

High Molecular Weight ◽

Rough Endoplasmic Reticulum ◽

Growth Pattern ◽

Literature Search ◽

Tumor Tissue ◽

Pleomorphic Sarcoma ◽

Paracrystalline Inclusions ◽

Alpha 1 Antitrypsin

Many pleomorphic sarcomas with a storiform growth pattern have been classified as malignant fibrous histiocytomas (MFH) for the last 20 years. The diagnosis is debatable and has received much criticism of late since MFH is a diagnosis of exclusion; it has no definable, reproducible criteria for its diagnosis. The advent of immunocytochemistry has established that nonspecific antibodies to alpha-1-antitrypsin and alpha-1-chymotrypsin will commonly react with these neoplasms. However, these antibodies are not reliable markers as they are 1) nonspecific and 2) not always reactive. It has been proposed that with sufficient effort in investigating these sometimes bizarre sarcomas, a more precise differentiation may be determined. We have recently examined a primitive sarcoma which could have been classified as MFH on the basis of histologic presentation (Figure 1), however, the tumor tissue reacted in an unusual manner with antibodies to high molecular weight keratin, vimentin, alpha-1-antitrypsin and alpha-1-chymotrypsin. Furthermore, significant accumulations of paracrystalline arrays (Figure 2) were found within the cisternae of the rough endoplasmic reticulum (RER). These findings led to a literature search in which we found that similar observations have been described in pediatric fibroblastic neoplasms.

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Microtubule motors and other maps

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010015753x ◽

1990 ◽

Vol 48 (3) ◽

pp. 1-1

Author(s):

Richard B. Vallee

Keyword(s):

Molecular Weight ◽

High Molecular Weight ◽

Cytoplasmic Dynein ◽

Organelle Transport ◽

Structural Components ◽

Microtubule Associated Proteins ◽

Microtubule Motors ◽

Associated Proteins ◽

The Subject ◽

Intracellular Motility

Microtubules are involved in a number of forms of intracellular motility, including mitosis and bidirectional organelle transport. Purified microtubules from brain and other sources contain tubulin and a diversity of microtubule associated proteins (MAPs). Some of the high molecular weight MAPs - MAP 1A, 1B, 2A, and 2B - are long, fibrous molecules that serve as structural components of the cytamatrix. Three MAPs have recently been identified that show microtubule activated ATPase activity and produce force in association with microtubules. These proteins - kinesin, cytoplasmic dynein, and dynamin - are referred to as cytoplasmic motors. The latter two will be the subject of this talk.Cytoplasmic dynein was first identified as one of the high molecular weight brain MAPs, MAP 1C. It was determined to be structurally equivalent to ciliary and flagellar dynein, and to produce force toward the minus ends of microtubules, opposite to kinesin.

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