Regulation of HMG-CoA Reductase Degradation Requires the P-Type ATPase Cod1p/Spf1p

doi:10.1083/jcb.148.5.915

This Article

	Full Text
	Full Text (PDF, 324K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Cronin, S. R.
	Articles by Hampton, R. Y.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Cronin, S. R.
	Articles by Hampton, R. Y.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0021-9525/2000/3/915/ $5.00
The Journal of Cell Biology, Volume 148, Number 5, March 6, 2000 915-924

Original Article

Regulation of HMG-CoA Reductase Degradation Requires the P-Type ATPase Cod1p/Spf1p

Stephen R. Cronin^a, Afif Khoury^a, Dana K. Ferry^a, and Randolph Y. Hampton^a
^a Department of Biology, University of California San Diego, La Jolla, California, 92093-0347

Correspondence to: Randolph Y. Hampton, UCSD Department of Biology, 9500 Gilman Dr. #0347, La Jolla, CA 92093-0347. Tel:(858) 822-0511 Fax:(858) 534-0555 E-mail:rhampton{at}biomail.ucsd.edu.

The integral ER membrane protein HMG-CoA reductase (HMGR) isa key enzyme of the mevalonate pathway from which sterols andother essential molecules are produced. HMGR degradation occursin the ER and is regulated by mevalonate-derived signals. Littleis known about the mechanisms responsible for regulating HMGRdegradation. The yeast Hmg2p isozyme of HMGR undergoes regulateddegradation in a manner very similar to mammalian HMGR, allowingus to isolate mutants deficient in regulating Hmg2p stability.We call these mutants cod mutants for the control of HMG-CoAreductase degradation. With this screen, we have identifiedthe first gene of this class, COD1, which encodes a P-type ATPaseand is identical to SPF1. Our data suggested that Cod1p is acalcium transporter required for regulating Hmg2p degradation.This role for Cod1p is distinctly different from that of thewell-characterized Ca²⁺ P-type ATPase Pmr1p which is neitherrequired for Hmg2p degradation nor its control. The identificationof Cod1p is especially intriguing in light of the role Ca²⁺plays in the regulated degradation of mammalian HMGR.

Key Words: hydroxymethylglutaryl CoA reductase, Ca²⁺-transporting ATPase,ubiquitin, endoplasmic reticulum, Saccharomyces cerevisiae

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Garza, R. M., Sato, B. K., Hampton, R. Y. (2009). In Vitro Analysis of Hrd1p-mediated Retrotranslocation of Its Multispanning Membrane Substrate 3-Hydroxy-3-methylglutaryl (HMG)-CoA Reductase. J. Biol. Chem. 284: 14710-14722 [Abstract] [Full Text]
Naito, M., Bomsztyk, K., Zager, R. A. (2009). Renal Ischemia-Induced Cholesterol Loading: Transcription Factor Recruitment and Chromatin Remodeling along the HMG CoA Reductase Gene. Am. J. Pathol. 174: 54-62 [Abstract] [Full Text]
Federovitch, C. M., Jones, Y. Z., Tong, A. H., Boone, C., Prinz, W. A., Hampton, R. Y. (2008). Genetic and Structural Analysis of Hmg2p-induced Endoplasmic Reticulum Remodeling in Saccharomyces cerevisiae. Mol. Biol. Cell 19: 4506-4520 [Abstract] [Full Text]
Bazirgan, O. A., Hampton, R. Y. (2008). Cue1p Is an Activator of Ubc7p E2 Activity in Vitro and in Vivo. J. Biol. Chem. 283: 12797-12810 [Abstract] [Full Text]
Bazirgan, O. A., Garza, R. M., Hampton, R. Y. (2006). Determinants of RING-E2 Fidelity for Hrd1p, a Membrane-anchored Ubiquitin Ligase. J. Biol. Chem. 281: 38989-39001 [Abstract] [Full Text]
Buvelot Frei, S., Rahl, P. B., Nussbaum, M., Briggs, B. J., Calero, M., Janeczko, S., Regan, A. D., Chen, C. Z., Barral, Y., Whittaker, G. R., Collins, R. N. (2006). Bioinformatic and comparative localization of rab proteins reveals functional insights into the uncharacterized GTPases ypt10p and ypt11p.. Mol. Cell. Biol. 26: 7299-7317 [Abstract] [Full Text]
Jakobsen,, M. K., Poulsen,, L. R., Schulz,, A., Fleurat-Lessard,, P., Moller,, A., Husted,, S., Schiott,, M., Amtmann,, A., Palmgren,, M. G. (2005). Pollen development and fertilization in Arabidopsis is dependent on the MALE GAMETOGENESIS IMPAIRED ANTHERS gene encoding a Type V P-type ATPase. Genes Dev. 19: 2757-2769 [Abstract] [Full Text]
de Martin, P. E., Du, Y., Novick, P., Ferro-Novick, S. (2005). Ice2p is important for the distribution and structure of the cortical ER network in Saccharomyces cerevisiae. J. Cell Sci. 118: 65-77 [Abstract] [Full Text]
Aiello, D. P., Fu, L., Miseta, A., Sipos, K., Bedwell, D. M. (2004). The Ca2+ Homeostasis Defects in a pgm2{Delta} Strain of Saccharomyces cerevisiae Are Caused by Excessive Vacuolar Ca2+ Uptake Mediated by the Ca2+-ATPase Pmc1p. J. Biol. Chem. 279: 38495-38502 [Abstract] [Full Text]
Vashist, S., Ng, D. T.W. (2004). Misfolded proteins are sorted by a sequential checkpoint mechanism of ER quality control. JCB 165: 41-52 [Abstract] [Full Text]
Shearer, A. G., Hampton, R. Y. (2004). Structural Control of Endoplasmic Reticulum-associated Degradation: EFFECT OF CHEMICAL CHAPERONES ON 3-HYDROXY-3-METHYLGLUTARYL-CoA REDUCTASE. J. Biol. Chem. 279: 188-196 [Abstract] [Full Text]
Wiederkehr, A., Du, Y., Pypaert, M., Ferro-Novick, S., Novick, P. (2003). Sec3p Is Needed for the Spatial Regulation of Secretion and for the Inheritance of the Cortical Endoplasmic Reticulum. Mol. Biol. Cell 14: 4770-4782 [Abstract] [Full Text]
Kellermayer, R., Aiello, D. P., Miseta, A., Bedwell, D. M. (2003). Extracellular Ca2+ sensing contributes to excess Ca2+ accumulation and vacuolar fragmentation in a pmr1{Delta} mutant of S. cerevisiae. J. Cell Sci. 116: 1637-1646 [Abstract] [Full Text]
Vashist, S., Frank, C. G., Jakob, C. A., Ng, D. T.W. (2002). Two Distinctly Localized P-Type ATPases Collaborate to Maintain Organelle Homeostasis Required for Glycoprotein Processing and Quality Control. Mol. Biol. Cell 13: 3955-3966 [Abstract] [Full Text]
Cronin, S. R., Rao, R., Hampton, R. Y. (2002). Cod1p/Spf1p is a P-type ATPase involved in ER function and Ca2+ homeostasis. JCB 157: 1017-1028 [Abstract] [Full Text]
Facanha, A. L. O., Appelgren, H., Tabish, M., Okorokov, L., Ekwall, K. (2002). The endoplasmic reticulum cation P-type ATPase Cta4p is required for control of cell shape and microtubule dynamics. JCB 157: 1029-1040 [Abstract] [Full Text]
Bonilla, M., Cunningham, K. W. (2002). Calcium Release and Influx in Yeast: TRPC and VGCC Rule Another Kingdom. Sci Signal 2002: pe17-pe17 [Abstract] [Full Text]
Du, Y., Pypaert, M., Novick, P., Ferro-Novick, S. (2001). Aux1p/Swa2p Is Required for Cortical Endoplasmic Reticulum Inheritance in Saccharomyces cerevisiae. Mol. Biol. Cell 12: 2614-2628 [Abstract] [Full Text]
Gardner, R. G., Shearer, A. G., Hampton, R. Y. (2001). In Vivo Action of the HRD Ubiquitin Ligase Complex: Mechanisms of Endoplasmic Reticulum Quality Control and Sterol Regulation. Mol. Cell. Biol. 21: 4276-4291 [Abstract] [Full Text]
Axelsen, K. B., Palmgren, M. G. (2001). Inventory of the Superfamily of P-Type Ion Pumps in Arabidopsis. Plant Physiol. 126: 696-706 [Abstract] [Full Text]
Gardner, R. G., Shan, H., Matsuda, S. P. T., Hampton, R. Y. (2001). An Oxysterol-derived Positive Signal for 3-Hydroxy- 3-methylglutaryl-CoA Reductase Degradation in Yeast. J. Biol. Chem. 276: 8681-8694 [Abstract] [Full Text]
Tipper, D. J., Harley, C. A (2002). Yeast Genes Controlling Responses to Topogenic Signals in a Model Transmembrane Protein. Mol. Biol. Cell 13: 1158-1174 [Abstract] [Full Text]